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Sample records for beta sheet formation

  1. Conformational diversity in prion protein variants influences intermolecular [beta]-sheet formation

    SciTech Connect

    Lee, Seungjoo; Antony, Lizamma; Hartmann, Rune; Knaus, Karen J.; Surewicz, Krystyna; Surewicz, Witold K.; Yee, Vivien C.

    2010-04-19

    A conformational transition of normal cellular prion protein (PrP{sup C}) to its pathogenic form (PrP{sup Sc}) is believed to be a central event in the transmission of the devastating neurological diseases known as spongiform encephalopathies. The common methionine/valine polymorphism at residue 129 in the PrP influences disease susceptibility and phenotype. We report here seven crystal structures of human PrP variants: three of wild-type (WT) PrP containing V129, and four of the familial variants D178N and F198S, containing either M129 or V129. Comparison of these structures with each other and with previously published WT PrP structures containing M129 revealed that only WT PrPs were found to crystallize as domain-swapped dimers or closed monomers; the four mutant PrPs crystallized as non-swapped dimers. Three of the four mutant PrPs aligned to form intermolecular {beta}-sheets. Several regions of structural variability were identified, and analysis of their conformations provides an explanation for the structural features, which can influence the formation and conformation of intermolecular {beta}-sheets involving the M/V129 polymorphic residue.

  2. Liquid Crystal Based Sensor to Detect Beta-Sheet Formation of Peptides

    NASA Astrophysics Data System (ADS)

    Sadati, Monirosadat; Izmitli Apik, Aslin; Abbott, Nicholas L.; de Pablo, Juan J.

    2015-03-01

    Protein aggregation into amyloid fibrils is involved in the progression of Alzheimer's, typeII diabetes and Huntington's diseases. Although larger aggregates remain important for clinical determination, small oligomers are of great interest due to their potentially toxic nature. It is therefore crucial to develop methods that probe the aggregation process at early stages and in the vicinity of biological membranes. Here, we present a simple method that relies on liquid crystalline materials and a Langmuir monolayer at the aqueous-liquid crystal (LC) interface. The approach is based on the LC's specific response to β-sheet structures, which abound in amyloid fibrils. When the system is observed under polarized light, the fibrils formed by amyloidogenic peptides give rise to the formation of elongated and branched structures in the LCs. Moreover, the PolScope measurements prove that the LCs are predominantly aligned along the fibrils when exposed to a β-sheet forming peptide. In contrast, non-amyloidogenic peptides form ellipsoidal domains of irregularly tilted LCs. This method is capable of reporting aggregation at lipid-aqueous interfaces at nanomolar concentrations of the peptide, and much earlier than commonly used fluorescence-based techniques. We thank Prof. Oleg D. Levrentovich and Young-Ki Kim from the Liquid Crystal Institute of Kent State University for the use of their PolScope instrument. This work was partially supported by the Swiss National Science Foundation (P300P2_151342).

  3. Sequence specificity, statistical potentials, and three-dimensional structure prediction with self-correcting distance geometry calculations of beta-sheet formation in proteins.

    PubMed Central

    Zhu, H.; Braun, W.

    1999-01-01

    A statistical analysis of a representative data set of 169 known protein structures was used to analyze the specificity of residue interactions between spatial neighboring strands in beta-sheets. Pairwise potentials were derived from the frequency of residue pairs in nearest contact, second nearest and third nearest contacts across neighboring beta-strands compared to the expected frequency of residue pairs in a random model. A pseudo-energy function based on these statistical pairwise potentials recognized native beta-sheets among possible alternative pairings. The native pairing was found within the three lowest energies in 73% of the cases in the training data set and in 63% of beta-sheets in a test data set of 67 proteins, which were not part of the training set. The energy function was also used to detect tripeptides, which occur frequently in beta-sheets of native proteins. The majority of native partners of tripeptides were distributed in a low energy range. Self-correcting distance geometry (SECODG) calculations using distance constraints sets derived from possible low energy pairing of beta-strands uniquely identified the native pairing of the beta-sheet in pancreatic trypsin inhibitor (BPTI). These results will be useful for predicting the structure of proteins from their amino acid sequence as well as for the design of proteins containing beta-sheets. PMID:10048326

  4. The Promiscuity of [beta]-Strand Pairing Allows for Rational Design of [beta]-Sheet Face Inversion

    SciTech Connect

    Makabe, Koki; Koide, Shohei

    2009-06-17

    Recent studies suggest the dominant role of main-chain H-bond formation in specifying {beta}-sheet topology. Its essentially sequence-independent nature implies a large degree of freedom in designing {beta}-sheet-based nanomaterials. Here we show rational design of {beta}-sheet face inversions by incremental deletions of {beta}-strands from the single-layer {beta}-sheet of Borrelia outer surface protein A. We show that a {beta}-sheet structure can be maintained when a large number of native contacts are removed and that one can design large-scale conformational transitions of a {beta}-sheet such as face inversion by exploiting the promiscuity of strand-strand interactions. High-resolution X-ray crystal structures confirmed the success of the design and supported the importance of main-chain H-bonds in determining {beta}-sheet topology. This work suggests a simple but effective strategy for designing and controlling nanomaterials based on {beta}-rich peptide self-assemblies.

  5. Study on the binding of Thioflavin T to beta-sheet-rich and non-beta-sheet cavities.

    PubMed

    Groenning, Minna; Olsen, Lars; van de Weert, Marco; Flink, James M; Frokjaer, Sven; Jørgensen, Flemming S

    2007-06-01

    Amyloid fibril formation plays a role in more than 20 diseases including Alzheimer's disease. In vitro detection of these fibrils is often performed using Thioflavin T (ThT), though the ThT binding mode is largely unknown. In the present study, spectral properties of ThT in binding environments representing beta-sheet-rich and non-beta-sheet cavities were examined. Acetylcholinesterase and gamma-cyclodextrin induced a characteristic ThT fluorescence similar to that with amyloid fibrils, whereas beta-cyclodextrin and the beta-sheet-rich transthyretin did not. The cavities of acetylcholinesterase and gamma-cyclodextrin were of similar diameter and only these cavities could accommodate two ThT ions according to molecular modelling. Binding stoichiometry studies also showed a possible binding of two ThT ions. Thus, the characteristic ThT fluorescence is induced in cavities with a diameter of 8-9A and a length able to accommodate the entire length of the ThT ion. The importance of a cavity diameter capable of binding two ThT ions, among others, indicates that an excimer formation is a plausible mechanism for the characteristic fluorescence. We propose a similar ThT binding mode in amyloid fibrils, where cavities of an appropriate size running parallel to the fibril axis have previously been proposed in several amyloid fibril models. PMID:17289401

  6. Amyloid Beta Mediates Memory Formation

    ERIC Educational Resources Information Center

    Garcia-Osta, Ana; Alberini, Cristina M.

    2009-01-01

    The amyloid precursor protein (APP) undergoes sequential cleavages to generate various polypeptides, including the amyloid [beta] (1-42) peptide (A[beta][1-42]), which is believed to play a major role in amyloid plaque formation in Alzheimer's disease (AD). Here we provide evidence that, in contrast with its pathological role when accumulated,…

  7. Structural principles for the propeller assembly of beta-sheets: the preference for seven-fold symmetry.

    PubMed

    Murzin, A G

    1992-10-01

    Twisted beta-sheets, packed face to face, may be arranged in circular formation like blades of a propeller or turbine. This beta-propeller fold has been found in three proteins: that in neuraminidase consists of six beta-sheets while those in methylamine dehydrogenase and galactose oxidase are composed of seven beta-sheets. A model for multisheet packing in the beta-propeller fold is proposed. This model gives both geometrical parameters of the beta-propellers composed of different numbers of sheets and patterns of residue packing at their sheet-to-sheet interfaces. All the known beta-propeller structures have been analyzed, and the observed geometries and residue packing are found to be in good agreement with those predicted by models. It is shown that unusual seven-fold symmetry is preferable to six- or eight-fold symmetry for propeller-like multi-sheet assembly. According to the model, a six-beta-sheet propeller has to have predominantly small residues in the beta-strands closed to its six-fold axis, but no strong sequence constraints are necessary for a seven-fold beta-propeller. PMID:1409568

  8. Beating the Heat - Fast Scanning Melts Silk Beta Sheet Crystals

    NASA Astrophysics Data System (ADS)

    Cebe, Peggy; Hu, Xiao; Kaplan, David L.; Zhuravlev, Evgeny; Wurm, Andreas; Arbeiter, Daniela; Schick, Christoph

    2013-01-01

    Beta-pleated-sheet crystals are among the most stable of protein secondary structures, and are responsible for the remarkable physical properties of many fibrous proteins, such as silk, or proteins forming plaques as in Alzheimer's disease. Previous thinking, and the accepted paradigm, was that beta-pleated-sheet crystals in the dry solid state were so stable they would not melt upon input of heat energy alone. Here we overturn that assumption and demonstrate that beta-pleated-sheet crystals melt directly from the solid state to become random coils, helices, and turns. We use fast scanning chip calorimetry at 2,000 K/s and report the first reversible thermal melting of protein beta-pleated-sheet crystals, exemplified by silk fibroin. The similarity between thermal melting behavior of lamellar crystals of synthetic polymers and beta-pleated-sheet crystals is confirmed. Significance for controlling beta-pleated-sheet content during thermal processing of biomaterials, as well as towards disease therapies, is envisioned based on these new findings.

  9. Engineering of betabellin 14D: disulfide-induced folding of a beta-sheet protein.

    PubMed Central

    Yan, Y.; Erickson, B. W.

    1994-01-01

    The betabellin target structure consists of 2 32-residue beta sheets packed against each other by hydrophobic interactions. We have designed, chemically synthesized, and biophysically characterized betabellin 14S, a single chain, and betabellin 14D, the disulfide-bridged double chain. The 32-residue nongenetic betabellin-14 chain (HSLTASIkaLTIHVQakTATCQVkaYTVHISE, a = D-Ala, k = D-Lys) has a palindromic pattern of polar (p), nonpolar (n), end (e), and beta-turn (t,r) residues (epnpnpnttnpnpnprrpnpnpnttnpnpnpe). Each half contains the same 14-residue palindromic pattern (underlined). Pairs of D-amino acid residues are used to favor formation of inverse-common (type-I') beta turns. In water at pH 6.5, the single chain of betabellin 14S is not folded, but the disulfide-linked betabellin 14D is folded into a stable beta-sheet structure. Thus, folding of the covalent dimer beta-bellin 14D is induced by formation of the single interchain disulfide bond. The binary pattern of alternating polar and nonpolar residues of its beta-sheets is not sufficient to induce folding. Betabellin 14D is a very water-soluble (10 mg/mL), small (64 residues), nongenetic (12 D residues) beta-sheet protein with properties (well-dispersed proton NMR resonances; Tm = 58 degrees C and delta Hm = 106 kcal/mol at pH 5.5) like those of a native protein structure. PMID:7920252

  10. Beating the Heat: Fast Scanning Melts Beta Sheet Crystals

    NASA Astrophysics Data System (ADS)

    Cebe, Peggy; Hu, Xiao; Kaplan, David; Zhuravlev, Evgeny; Wurm, Andreas; Arbeiter, Daniella; Schick, Christoph

    2014-03-01

    Beta-pleated-sheet crystals are among the most stable of protein secondary structures, and are responsible for the remarkable physical properties of many fibrous proteins, such as silk. Previous thinking was that beta-pleated-sheet crystals in the dry solid state would not melt upon input of heat energy alone. Indeed, at conventional heating rates (~1-50 °C/min), silk exhibits its glass transition (~175 °C), followed by cold crystallization, and then by immediate thermal degradation beginning at about 225 °C. Here we demonstrate that beta-pleated-sheet crystals can melt directly from the solid state to become random coils, helices, and turns. We use fast scanning chip calorimetry at 2,000 K/s to avoid thermal degradation, and report the first reversible thermal melting of protein beta-pleated-sheet crystals, exemplified by silk fibroin. The similarity between thermal melting behavior of lamellar crystals of synthetic polymers and beta-pleated-sheet crystals is confirmed. The authors acknowledge support from the National Science Foundation and German Academic Exchange Service DAAD; EZ acknowledges a European Union funded Marie Curie EST fellowship (ADVATEC); XH and DK acknowledge NIH P41 Tissue Engineering Resource Center.

  11. High beta plasma in the dynamic Jovian current sheet

    NASA Technical Reports Server (NTRS)

    Walker, R. J.; Kivelson, M. G.; Schardt, A. W.

    1978-01-01

    The equatorial current sheet, which Pioneer 10 repeatedly encountered on its outbound pass through the Jovian magnetosphere, frequently was associated with intense fluxes of energetic protons. Simultaneous observations of the changes in the energetic proton flux and in the magnetic-field magnitude demonstrate that the current sheet is embedded in a high-beta plasma in which high-energy (above 60 keV) ions frequently are the dominant constituents. Large differences in the plasma temperature and the thickness of this plasma sheet between encounters only 10 hours apart indicate that the Jovian plasma sheet is very dynamic on a time scale of hours. Occasional observations of significant temporal variations in the magnetic field and particle populations during periods within the plasma sheet may represent in situ observations of Jovian magnetic disturbances. Comparison with previous observations suggests that low-energy (not more than 5 keV) plasma contributes less than 3% to the current-sheet energy density.

  12. Evidence for Novel [beta]-Sheet Structures in Iowa Mutant [beta]-Amyloid Fibrils

    SciTech Connect

    Tycko, Robert; Sciarretta, Kimberly L.; Orgel, Joseph P.R.O.; Meredith, Stephen C.

    2009-07-24

    Asp23-to-Asn mutation within the coding sequence of {beta}-amyloid, called the Iowa mutation, is associated with early onset, familial Alzheimer's disease and cerebral amyloid angiopathy, in which patients develop neuritic plaques and massive vascular deposition predominantly of the mutant peptide. We examined the mutant peptide, D23N-A{beta}40, by electron microscopy, X-ray diffraction, and solid-state NMR spectroscopy. D23N-A{beta}40 forms fibrils considerably faster than the wild-type peptide (k = 3.77 x 10{sup -3} min{sup -1} and 1.07 x 10{sup -4} min{sup -1} for D23N-A{beta}40 and the wild-type peptide WT-A{beta}40, respectively) and without a lag phase. Electron microscopy shows that D23N-A{beta}40 forms fibrils with multiple morphologies. X-ray fiber diffraction shows a cross-{beta} pattern, with a sharp reflection at 4.7 {angstrom} and a broad reflection at 9.4 {angstrom}, which is notably smaller than the value for WT-A{beta}40 fibrils (10.4 {angstrom}). Solid-state NMR measurements indicate molecular level polymorphism of the fibrils, with only a minority of D23N-A{beta}40 fibrils containing the in-register, parallel {beta}-sheet structure commonly found in WT-A{beta}40 fibrils and most other amyloid fibrils. Antiparallel {beta}-sheet structures in the majority of fibrils are indicated by measurements of intermolecular distances through 13C-13C and 15N-13C dipole-dipole couplings. An intriguing possibility exists that there is a relationship between the aberrant structure of D23N-A{beta}40 fibrils and the unusual vasculotropic clinical picture in these patients.

  13. Reversible thermal denaturation of a 60-kDa genetically engineered beta-sheet polypeptide.

    PubMed

    Lednev, Igor K; Ermolenkov, Vladimir V; Higashiya, Seiichiro; Popova, Ludmila A; Topilina, Natalya I; Welch, John T

    2006-11-15

    A de novo 687-amino-acid residue polypeptide with a regular 32-amino-acid repeat sequence, (GA)(3)GY(GA)(3)GE(GA)(3)GH(GA)(3)GK, forms large beta-sheet assemblages that exhibit remarkable folding properties and, as well, form fibrillar structures. This construct is an excellent tool to explore the details of beta-sheet formation yielding intimate folding information that is otherwise difficult to obtain and may inform folding studies of naturally occurring materials. The polypeptide assumes a fully folded antiparallel beta-sheet/turn structure at room temperature, and yet is completely and reversibly denatured at 125 degrees C, adopting a predominant polyproline II conformation. Deep ultraviolet Raman spectroscopy indicated that melting/refolding occurred without any spectroscopically distinct intermediates, yet the relaxation kinetics depend on the initial polypeptide state, as would be indicative of a non-two-state process. Thermal denaturation and refolding on cooling appeared to be monoexponential with characteristic times of approximately 1 and approximately 60 min, respectively, indicating no detectable formation of hairpin-type nuclei in the millisecond timescale that could be attributed to nonlocal "nonnative" interactions. The polypeptide folding dynamics agree with a general property of beta-sheet proteins, i.e., initial collapse precedes secondary structure formation. The observed folding is much faster than expected for a protein of this size and could be attributed to a less frustrated free-energy landscape funnel for folding. The polypeptide sequence suggests an important balance between the absence of strong nonnative contacts (salt bridges or hydrophobic collapse) and limited repulsion of charged side chains. PMID:16891363

  14. Role of Polyalanine Domains in -Sheet Formation in Spider Silk Block Copolymers

    SciTech Connect

    Rabotyagova, O.; Cebe, P; Kaplan, D

    2010-01-01

    Genetically engineered spider silk-like block copolymers were studied to determine the influence of polyalanine domain size on secondary structure. The role of polyalanine block distribution on {beta}-sheet formation was explored using FT-IR and WAXS. The number of polyalanine blocks had a direct effect on the formation of crystalline {beta}-sheets, reflected in the change in crystallinity index as the blocks of polyalanines increased. WAXS analysis confirmed the crystalline nature of the sample with the largest number of polyalanine blocks. This approach provides a platform for further exploration of the role of specific amino acid chemistries in regulating the assembly of {beta}-sheet secondary structures, leading to options to regulate material properties through manipulation of this key component in spider silks.

  15. Formation of Sprays From Conical Liquid Sheets

    NASA Technical Reports Server (NTRS)

    Peck, Bill; Mansour, N. N.; Koga, Dennis (Technical Monitor)

    1999-01-01

    Our objective is to predict droplet size distributions created by fuel injector nozzles in Jet turbines. These results will be used to determine the initial conditions for numerical simulations of the combustion process in gas turbine combustors. To predict the droplet size distribution, we are currently constructing a numerical model to understand the instability and breakup of thin conical liquid sheets. This geometry serves as a simplified model of the liquid jet emerging from a real nozzle. The physics of this process is difficult to study experimentally as the time and length scales are very short. From existing photographic data, it does seem clear that three-dimensional effects such as the formation of streamwise ligaments and the pulling back of the sheet at its edges under the action of surface tension are important.

  16. A recipe for designing water-soluble, beta-sheet-forming peptides.

    PubMed Central

    Mayo, K. H.; Ilyina, E.; Park, H.

    1996-01-01

    Based on observations of solubility and folding properties of peptide 33-mers derived from the beta-sheet domains of platelet factor-4 (PF4), interleukin-8 (IL-8), and growth related protein (Gro-alpha), as well as other beta-sheet-forming peptides, general guidelines have been developed to aid in the design of water soluble, self-association-induced beta-sheet-forming peptides. CD, 1H-NMR, and pulsed field gradient NMR self-diffusion measurements have been used to assess the degree of folding and state of aggregation. PF4 peptide forms native-like beta-sheet tetramers and is sparingly soluble above pH 6. IL-8 peptide is insoluble between pH 4.5 and pH 7.5, yet forms stable, native-like beta-sheet dimers at higher pH. Gro-alpha peptide is soluble at all pH values, yet displays no discernable beta-sheet structure even when diffusion data indicate dimer-tetramer aggregation. A recipe used in the de novo design of water-soluble beta-sheet-forming peptides calls for the peptide to contain 40-50% hydrophobic residues, usually aliphatic ones (I, L, V, A, M) (appropriately paired and mostly but not always alternating with polar residues in the sheet sequence), a positively charged (K, R) to negatively charged (E, D) residue ratio between 4/2 and 6/2, and a noncharged polar residue (N, Q, T, S) composition of about 20% or less. Results on four de novo designed, 33-residue peptides are presented supporting this approach. Under near physiologic conditions, all four peptides are soluble, form beta-sheet structures to varying degrees, and self-associate. One peptide folds as a stable, compact beta-sheet tetramer, whereas the others are transient beta-sheet-containing aggregates. PMID:8819163

  17. Spectroscopic studies of structural changes in two beta-sheet-forming peptides show an ensemble of structures that unfold noncooperatively.

    PubMed

    Kuznetsov, Serguei V; Hilario, Jovencio; Keiderling, Timothy A; Ansari, Anjum

    2003-04-22

    A characterization of the conformation and stability of model peptide systems that form beta-sheets in aqueous solutions is considerably important in gaining insights into the mechanism of beta-sheet formation in proteins. We have characterized the conformation and equilibrium folding and unfolding of two 20-residue peptides whose NMR spectra suggest a three-stranded beta-sheet topology in aqueous solution: Betanova [Kortemme, T., Ramirez-Alvarado, M., and Serrano, L. (1998) Science 281, 253-256] and (D)P(D)P with d-Pro-Gly segments at the turns [Schenck, H. L., and Gellman, S. H. (1998) J. Am. Chem. Soc. 120, 4869-4870]. Both circular dichroism (CD) and infrared measurements indicate only 20-26% beta-sheet-like structure at 5 degrees C for Betanova and 42-59% beta-sheet for (D)P(D)P. For both peptides, the CD and infrared spectra change nearly linearly with increasing temperatures (or urea concentrations) and lack a sigmoidal signature characteristic of cooperative unfolding. Fluorescence resonance energy transfer (FRET) measurements between donor and acceptor molecules attached to the two ends confirm that Betanova is largely unstructured even at 10 degrees C; the average end-to-end distance estimated from FRET is closer to that of a random coil than a structured beta-sheet. In (D)P(D)P, the FRET results indicate a more compact structure that remains compact even at high temperatures (approximately 80 degrees C) or high urea concentrations (approximately 8 M). These results indicate that both these peptides access an ensemble of conformations at all temperatures or denaturant concentrations, with no significant free energy barrier separating the "folded" and "unfolded" conformations.

  18. Evidence for novel beta-sheet structures in Iowa mutant beta-amyloid fibrils.

    PubMed

    Tycko, Robert; Sciarretta, Kimberly L; Orgel, Joseph P R O; Meredith, Stephen C

    2009-07-01

    Asp23-to-Asn mutation within the coding sequence of beta-amyloid, called the Iowa mutation, is associated with early onset, familial Alzheimer's disease and cerebral amyloid angiopathy, in which patients develop neuritic plaques and massive vascular deposition predominantly of the mutant peptide. We examined the mutant peptide, D23N-Abeta40, by electron microscopy, X-ray diffraction, and solid-state NMR spectroscopy. D23N-Abeta40 forms fibrils considerably faster than the wild-type peptide (k = 3.77 x 10(-3) min(-1) and 1.07 x 10(-4) min(-1) for D23N-Abeta40 and the wild-type peptide WT-Abeta40, respectively) and without a lag phase. Electron microscopy shows that D23N-Abeta40 forms fibrils with multiple morphologies. X-ray fiber diffraction shows a cross-beta pattern, with a sharp reflection at 4.7 A and a broad reflection at 9.4 A, which is notably smaller than the value for WT-Abeta40 fibrils (10.4 A). Solid-state NMR measurements indicate molecular level polymorphism of the fibrils, with only a minority of D23N-Abeta40 fibrils containing the in-register, parallel beta-sheet structure commonly found in WT-Abeta40 fibrils and most other amyloid fibrils. Antiparallel beta-sheet structures in the majority of fibrils are indicated by measurements of intermolecular distances through (13)C-(13)C and (15)N-(13)C dipole-dipole couplings. An intriguing possibility exists that there is a relationship between the aberrant structure of D23N-Abeta40 fibrils and the unusual vasculotropic clinical picture in these patients.

  19. Precise assembly of complex beta sheet topologies from de novo designed building blocks

    PubMed Central

    King, Indigo Chris; Gleixner, James; Doyle, Lindsey; Kuzin, Alexandre; Hunt, John F; Xiao, Rong; Montelione, Gaetano T; Stoddard, Barry L; DiMaio, Frank; Baker, David

    2015-01-01

    Design of complex alpha-beta protein topologies poses a challenge because of the large number of alternative packing arrangements. A similar challenge presumably limited the emergence of large and complex protein topologies in evolution. Here, we demonstrate that protein topologies with six and seven-stranded beta sheets can be designed by insertion of one de novo designed beta sheet containing protein into another such that the two beta sheets are merged to form a single extended sheet, followed by amino acid sequence optimization at the newly formed strand-strand, strand-helix, and helix-helix interfaces. Crystal structures of two such designs closely match the computational design models. Searches for similar structures in the SCOP protein domain database yield only weak matches with different beta sheet connectivities. A similar beta sheet fusion mechanism may have contributed to the emergence of complex beta sheets during natural protein evolution. DOI: http://dx.doi.org/10.7554/eLife.11012.001 PMID:26650357

  20. Propagating structure of alzheimer's {beta}-amyloid is parallel {beta}-sheet with residues in exact register.

    SciTech Connect

    Benzinger, T. L. S.; Gregory, D. M.; Burkoth, T. S.; Miller-Auer, H.; Lynn, D. G.; Botto, R. E.; Meredith, S. C.; Chemistry; Univ. of Chicago

    1998-11-10

    The pathognomonic plaques of Alzheimer's disease are composed primarily of the 39- to 43-aa {beta}-amyloid (A{beta}) peptide. Crosslinking of A{beta} peptides by tissue transglutaminase (tTg) indicates that Gln15 of one peptide is proximate to Lys16 of another in aggregated A{beta}. Here we report how the fibril structure is resolved by mapping interstrand distances in this core region of the A{beta} peptide chain with solid-state NMR. Isotopic substitution provides the source points for measuring distances in aggregated A{beta}. Peptides containing a single carbonyl 13C label at Gln15, Lys16, Leu17, or Val18 were synthesized and evaluated by NMR dipolar recoupling methods for the measurement of interpeptide distances to a resolution of 0.2 Angstrom. Analysis of these data establish that this central core of A{beta} consists of a parallel {beta}-sheet structure in which identical residues on adjacent chains are aligned directly, i.e., in register. Our data, in conjunction with existing structural data, establish that the A{beta} fibril is a hydrogen-bonded, parallel {beta}-sheet defining the long axis of the A{beta} fibril propagation.

  1. Cluster observes formation of high-beta plasma blobs

    NASA Astrophysics Data System (ADS)

    Haerendel, G.; Georgescu, E.; Glassmeier, K. H.; Klecker, B.; Bogdanova, J.; Reme, H.; Frey, H. U.; Vaivads, A.

    2003-04-01

    Late in a sequence of four moderate substorms an 26 July 2001, Cluster observed periods of a few minutes durations of high-beta plasma events (B < 10nT, beta = 2 - 30), connected with dipolarizations of the magnetic field. Cluster was located near 02:45 MLT, at R = 19 Re and at about 5 degrees N GSM. These events began late in the recovery phase of the second and about 5 minutes before onset of the third substorm and lasted for three hours, way beyond the recovery phase of the fourth substorm. The most remarkable observation is that the onset coincided with the arrival of energetic (E ~ 7 keV) O+ ions from the ionosphere, which tended to dominate the plasma composition throughout the remaining time. The magnetic flux and the transverse plasma transport is continuously directed equator- and earthward with oscillatory east-west movements superposed. Periods of order 5 - 10 minutes and strong correlations between the magnetic elevation angle and log(beta) (correlation coefficient 0.78) are highly reminiscent of the high-beta plasma blobs discovered with Equator-S and Geotail between 9 and 11 Re in the late night/early morning sector [Haerendel et al. 1999]. Another feature in common with the Equator-S and Geotail observations is the plasma flow towards low latitudes during the magnetic field recovery. We conclude that Cluster observed the plasma blob formation in the tail plasma sheet, which seems to occur dominantly in the recovery and post-recovery phase of substorms. This is consistent with the finding of Equator-S and Geotail. The origin is a pulsed earthward plasma transport with velocity amplitudes of only several tens of km/s. It needs to be investigated whether the preceeding injection of ionospheric O+ ions into the plasma sheet plays a causal role in the process.

  2. Design and construction of an open multistranded beta-sheet polypeptide stabilized by a disulfide bridge.

    PubMed

    Venkatraman, Janani; Nagana Gowda, Gowda A; Balaram, Padmanabhan

    2002-05-01

    The design and characterization of an open eight-stranded beta-sheet in a synthetic, 2-fold symmetric 70-residue peptide is described. The design strategy involves the generation of a 35-residue four-stranded beta-sheet peptide in which successive hairpins are nucleated by appropriately positioned (D)Pro-Xxx sequences. Oxidative dimerization using a single Cys residue positioned at the center of the C-terminal strand results in a disulfide-bridged eight-stranded structure. Nuclear Overhauser effects firmly establish an eight-stranded beta-sheet in methanol. In water, the outer strands are frayed, but a well-defined four-stranded beta-sheet stabilized by a disulfide bridge and a hydrophobic cluster is determined from NMR data. Comparison of the precursor peptide with the disulfide-bridged dimer reveals considerable enhancement of beta-sheet content in the latter, suggesting that the disulfide cross-link is an effective strategy for the stabilization of beta-sheets.

  3. Copper abolishes the beta-sheet secondary structure of preformed amyloid fibrils of amyloid-beta(42).

    PubMed

    House, Emily; Mold, Matthew; Collingwood, Joanna; Baldwin, Alex; Goodwin, Steven; Exley, Christopher

    2009-01-01

    The observation of the co-deposition of metals and amyloid-beta(42) (Abeta(42)) in brain tissue in Alzheimer's disease prompted myriad investigations into the role played by metals in the precipitation of this peptide. Copper is bound by monomeric Abeta(12) and upon precipitation of the copper-peptide complex thereby prevents Abeta(42) from adopting a beta-sheet secondary structure. Copper is also bound by beta-sheet conformers of Abeta(42), and herein we have investigated how this interaction affects the conformation of the precipitated peptide. Copper significantly reduced the thioflavin T fluorescence of aged, fibrillar Abeta(42) with, for example, a 20-fold excess of the metal resulting in a ca 90% reduction in thioflavin T fluorescence. Transmission electron microscopy showed that copper significantly reduced the quantities of amyloid fibrils while Congo red staining and polarized light demonstrated a copper-induced abolition of apple-green birefringence. Microscopy under cross-polarized light also revealed the first observation of spherulites of Abeta(42). The size and appearance of these amyloid structures were found to be very similar to spherulites identified in Alzheimer's disease tissue. The combined results of these complementary methods strongly suggested that copper abolished the beta-sheet secondary structure of pre-formed, aged amyloid fibrils of Abeta(42). Copper may protect against the presence of beta-sheets of Abeta(42) in vivo, and its binding by fibrillar Abeta(42) could have implications for Alzheimer's disease therapy. PMID:19749401

  4. Conversion of non-fibrillar {beta}-sheet oligomers into amyloid fibrils in Alzheimer's disease amyloid peptide aggregation

    SciTech Connect

    Benseny-Cases, Nuria; Cocera, Mercedes; Cladera, Josep

    2007-10-05

    A{beta}(1-40) is one of the main components of the fibrils found in amyloid plaques, a hallmark of brains affected by Alzheimer's disease. It is known that prior to the formation of amyloid fibrils in which the peptide adopts a well-ordered intermolecular {beta}-sheet structure, peptide monomers associate forming low and high molecular weight oligomers. These oligomers have been previously described in electron microscopy, AFM, and exclusion chromatography studies. Their specific secondary structures however, have not yet been well established. A major problem when comparing aggregation and secondary structure determinations in concentration-dependent processes such as amyloid aggregation is the different concentration range required in each type of experiment. In the present study we used the dye Thioflavin T (ThT), Fourier-transform infrared spectroscopy, and electron microscopy in order to structurally characterize the different aggregated species which form during the A{beta}(1-40) fibril formation process. A unique sample containing 90 {mu}M peptide was used. The results show that oligomeric species which form during the lag phase of the aggregation kinetics are a mixture of unordered, helical, and intermolecular non-fibrillar {beta}-structures. The number of oligomers and the amount of non-fibrillar {beta}-structures grows throughout the lag phase and during the elongation phase these non-fibrillar {beta}-structures are transformed into fibrillar (amyloid) {beta}-structures, formed by association of high molecular weight intermediates.

  5. Chain length scaling of protein folding time: Beta sheet structures

    NASA Astrophysics Data System (ADS)

    Dimitrievski, K.; Kasemo, B.; Zhdanov, V. P.

    2000-07-01

    We present comprehensive 3D lattice Monte Carlo simulations of the folding kinetics of two-turn antiparallel β sheets. The model employed takes into account isotropic nonspecific interactions as in previous flexible heteropolymer models and also orientation-dependent monomer-monomer interactions, mimicking the formation of hydrogen bonds and chain rigidity. The chain length is varied from N=15 to 33. For each chain length, we calculate the fastest folding temperature, Tfast, folding temperature, Tfold, and glass-transition temperature, Tg. The time-averaged occupation probability of the native state is found to be nearly independent of N at all temperatures. The dependence of Tfast and Tfold on N is accordingly relatively weak. The temperature interval where the folding is fast rapidly decreases with increasing N. For the chain lengths chosen, Tfold slightly exceeds Tg. The dependence of the folding time τf on N is well fitted by using the power law, τf∝Nλ. The exponent λ is found to depend on temperature and on the distribution of nonspecific interactions in the chain. In particular, λ=2.7-4.0 at T=Tfast and 5.2 at T slightly below Tfold. Evaluating τf in real units at T near Tfold yields physically reasonable results.

  6. Structural characterization of adsorbed helical and beta-sheet peptides

    NASA Astrophysics Data System (ADS)

    Samuel, Newton Thangadurai

    Adsorbed peptides on surfaces have potential applications in the fields of biomaterials, tissue engineering, peptide microarrays and nanobiotechnology. The surface region, the "biomolecular interface" between a material and the biological environment, plays a crucial role in these applications. As a result, characterization of adsorbed peptide structure, especially with respect to identity, concentration, spatial distribution, conformation and orientation, is important. The present research employs NEXAFS (near-edge X-ray absorption fine structure spectroscopy) and SFG (sum frequency generation spectroscopy) to provide information about the adsorbed peptide structure. Soft X-ray NEXAFS is a synchrotron-based technique which typically utilizes polarized X-rays to interrogate surfaces under ultra-high vacuum conditions. SFG is a non-linear optical technique which utilizes a combination of a fixed visible and a tunable infrared laser beams to generate a surface-vibrational spectrum of surface species. SFG has the added advantage of being able to directly analyze the surface-structure at the solid-liquid interface. The main goals of the present research were twofold: characterize the structure of adsorbed peptides (1) ex situ using soft X-ray NEXAFS, and (2) in situ using non-linear laser spectroscopy (SFG). Achieving the former goal involved first developing a comprehensive characterization of the carbon, nitrogen and oxygen k-edge NEXAFS spectra for amino acids, and then using a series of helical and beta-sheet peptides to demonstrate the sensitivity of polarization-dependent NEXAFS to secondary structure of adsorbed peptides. Characterizing the structure of adsorbed peptides in situ using SFG involved developing a model system to probe the solid-liquid interface in situ; demonstrating the ability to probe the molecular interactions and adsorbed secondary structure; following the time-dependent ordering of the adsorbed peptides; and establishing the ability to obtain

  7. Thickness of mouthguard sheets after vacuum-pressure formation: influence of mouthguard sheet material.

    PubMed

    Takahashi, Mutsumi; Koide, Kaoru; Iwasaki, Shin-Ichi

    2016-06-01

    The aim of this study was to investigate the thickness of mouthguard sheet after vacuum-pressure formation based on the mouthguard sheet material. Three mouthguard sheet materials (4.0 mm thick) were compared: ethylene-vinyl acetate co-polymer (EVA), olefin co-polymer (OL), and polyolefin-polystyrene co-polymer (OS). The working model was made by hard gypsum that was trimmed to the height of 20 mm at the cutting edge of the maxillary central incisor and 15 mm at the mesiobuccal cusp of the maxillary first molar. Where the center of the softened sheet sagged 15 mm lower than the clamp, the sheet was pressed against the working model, followed by vacuum forming for 10 s and compression molding for 2 min. The thickness of mouthguard sheets after fabrication was determined for the incisal portion (incisal edge and labial surface) and molar portion (cusp and buccal surface), and dimensional measurements were obtained using a measuring device. Differences in the change in thickness due to sheet materials were analyzed by one-way analysis of variance (anova) followed by Bonferroni's multiple comparison tests. The OL sheet was thickest at all measurement points. At the incisal edge and cusp, thickness after formation was highest for OL, then EVA and finally OS. At the labial surface and buccal surface, the thickness after formation was highest for OL, then OS and finally EVA. This study suggested that post-fabrication mouthguard thickness differed according to sheet material, with the olefin co-polymer sheet having the smallest thickness reduction.

  8. Numerical simulation of current sheet formation in a quasiseparatrix layer using adaptive mesh refinement

    SciTech Connect

    Effenberger, Frederic; Thust, Kay; Grauer, Rainer; Dreher, Juergen; Arnold, Lukas

    2011-03-15

    The formation of a thin current sheet in a magnetic quasiseparatrix layer (QSL) is investigated by means of numerical simulation using a simplified ideal, low-{beta}, MHD model. The initial configuration and driving boundary conditions are relevant to phenomena observed in the solar corona and were studied earlier by Aulanier et al. [Astron. Astrophys. 444, 961 (2005)]. In extension to that work, we use the technique of adaptive mesh refinement (AMR) to significantly enhance the local spatial resolution of the current sheet during its formation, which enables us to follow the evolution into a later stage. Our simulations are in good agreement with the results of Aulanier et al. up to the calculated time in that work. In a later phase, we observe a basically unarrested collapse of the sheet to length scales that are more than one order of magnitude smaller than those reported earlier. The current density attains correspondingly larger maximum values within the sheet. During this thinning process, which is finally limited by lack of resolution even in the AMR studies, the current sheet moves upward, following a global expansion of the magnetic structure during the quasistatic evolution. The sheet is locally one-dimensional and the plasma flow in its vicinity, when transformed into a comoving frame, qualitatively resembles a stagnation point flow. In conclusion, our simulations support the idea that extremely high current densities are generated in the vicinities of QSLs as a response to external perturbations, with no sign of saturation.

  9. The molecular organization of the beta-sheet region in Corneous beta-proteins (beta-keratins) of sauropsids explains its stability and polymerization into filaments.

    PubMed

    Calvaresi, Matteo; Eckhart, Leopold; Alibardi, Lorenzo

    2016-06-01

    The hard corneous material of avian and reptilian scales, claws, beak and feathers is mainly derived from the presence of proteins formerly known as beta-keratins but now termed Corneous beta-proteins of sauropsids to distinguish them from keratins, which are members of the intermediate filament protein family. The modeling of the conserved 34 amino acid residues long central beta-sheet region of Corneous beta-proteins using an ab initio protein folding and structure prediction algorithm indicates that this region is formed by four antiparallel beta-sheets. Molecular dynamic simulations and Molecular Mechanics/Poisson Boltzmann Surface Area (MM-PBSA) analysis showed that the disposition of polar and apolar amino acids within the beta-region gives rise to an amphipathic core whose stability is further increased, especially in an aqueous environment, by the association into a dimer due to apolar interactions and specific amino-acid interactions. The dimers in turn polymerize into a 3nm thick linear beta-filament due to van der Waals and hydrogen-bond interactions. It is suggested that once this nuclear core of anti-parallel sheets evolved in the genome of a reptilian ancestor of the extant reptiles and birds about 300 millions years ago, new properties emerged in the corneous material forming scales, claws, beaks and feathers in these amniotes based on the tendency of these unique corneous proteins to form stable filaments different from keratin intermediate filaments or sterical structures formed by other corneous proteins so far known.

  10. Formation of current sheets in magnetic reconnection

    SciTech Connect

    Boozer, Allen H.

    2014-07-15

    An ideal evolution of magnetic fields in three spatial dimensions tends to cause neighboring field lines to increase their separation exponentially with distance ℓ along the lines, δ(ℓ)=δ(0)e{sup σ(ℓ)}. The non-ideal effects required to break magnetic field line connections scale as e{sup −σ}, so the breaking of connections is inevitable for σ sufficiently large—even though the current density need nowhere be large. When the changes in field line connections occur rapidly compared to an Alfvén transit time, the constancy of j{sub ||}/B along the magnetic field required for a force-free equilibrium is broken in the region where the change occurs, and an Alfvénic relaxation of j{sub ||}/B occurs. Independent of the original spatial distribution of j{sub ||}/B, the evolution is into a sheet current, which is stretched by a factor e{sup σ} in width and contracted by a factor e{sup σ} in thickness with the current density j{sub ||} increasing as e{sup σ}. The dissipation of these sheet currents and their associated vorticity sheets appears to be the mechanism for transferring energy from a reconnecting magnetic field to a plasma. Harris sheets, which are used in models of magnetic reconnection, are shown to break up in the direction of current flow when they have a finite width and are in a plasma in force equilibrium. The dependence of the longterm nature of magnetic reconnection in systems driven by footpoint motion can be studied in a model that allows qualitative variation in the nature of that motion: slow or fast motion compared to the Alfvén transit time and the neighboring footpoints either exponentially separating in time or not.

  11. Multi-layer Parallel Beta-Sheet Structure of Amyloid Beta peptide (1-40) aggregate observed by discrete molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Peng, Shouyong; Urbanc, Brigita; Ding, Feng; Cruz, Luis; Buldyrev, Sergey; Dokholyan, Nikolay; Stanley, H. E.

    2003-03-01

    New evidence shows that oligomeric forms of Amyloid-Beta are potent neurotoxins that play a major role in neurodegeneration of Alzheimer's disease. Detailed knowledge of the structure and assembly dynamics of Amyloid-Beta is important for the development of new therapeutic strategies. Here we apply a two-atom model with Go interactions to model aggregation of Amyloid-Beta (1-40) peptides using the discrete molecular dynamics simulation. At temperatures above the transition temperature from an alpha-helical to random coil, we obtain two types of parallel beta-sheet structures, (a) a helical beta-sheet structure at a lower temperature and (b) a parallel beta-sheet structure at a higher temperature, both with inter-sheet distance of 10 A and with free edges which possibly enable further fibrillar elongation.

  12. Characteristics of Amyloid-Related Oligomers Revealed by Crystal Structures of Macrocyclic [beta]-Sheet Mimics

    SciTech Connect

    Liu, Cong; Sawaya, Michael R.; Cheng, Pin-Nan; Zheng, Jing; Nowick, James S.; Eisenberg, David

    2011-09-20

    Protein amyloid oligomers have been strongly linked to amyloid diseases and can be intermediates to amyloid fibers. {beta}-Sheets have been identified in amyloid oligomers. However, because of their transient and highly polymorphic properties, the details of their self-association remain elusive. Here we explore oligomer structure using a model system: macrocyclic peptides. Key amyloidogenic sequences from A{beta} and tau were incorporated into macrocycles, thereby restraining them to {beta}-strands, but limiting the growth of the oligomers so they may crystallize and cannot fibrillate. We determined the atomic structures for four such oligomers, and all four reveal tetrameric interfaces in which {beta}-sheet dimers pair together by highly complementary, dry interfaces, analogous to steric zippers found in fibers, suggesting a common structure for amyloid oligomers and fibers. In amyloid fibers, the axes of the paired sheets are either parallel or antiparallel, whereas the oligomeric interfaces display a variety of sheet-to-sheet pairing angles, offering a structural explanation for the heterogeneity of amyloid oligomers.

  13. Mechanical energy transfer and dissipation in fibrous beta-sheet-rich proteins.

    PubMed

    Xu, Zhiping; Buehler, Markus J

    2010-06-01

    Mechanical properties of structural protein materials are crucial for our understanding of biological processes and disease states. Through utilization of molecular simulation based on stress wave tracking, we investigate mechanical energy transfer processes in fibrous beta-sheet-rich proteins that consist of highly ordered hydrogen bond (H-bond) networks. By investigating four model proteins including two morphologies of amyloids, beta solenoids, and silk beta-sheet nanocrystals, we find that all beta-sheet-rich protein fibrils provide outstanding elastic moduli, where the silk nanocrystal reaches the highest value of ≈40 GPa. However, their capacities to dissipate mechanical energy differ significantly and are controlled strongly by the underlying molecular structure of H-bond network. Notably, silk beta-sheet nanocrystals feature a ten times higher energy damping coefficient than others, owing to flexible intrastrand motions in the transverse directions. The results demonstrate a unique feature of silk nanocrystals, their capacity to simultaneously provide extreme stiffness and energy dissipation capacity. Our results could help one to explain the remarkable properties of silks from an atomistic and molecular perspective, in particular its great toughness and energy dissipation capacity, and may enable the design of multifunctional nanomaterials with outstanding stiffness, strength, and impact resistance.

  14. Dynamics of sheet nacre formation in bivalves.

    PubMed

    Rousseau, Marthe; Meibom, Anders; Gèze, Marc; Bourrat, Xavier; Angellier, Martine; Lopez, Evelyne

    2009-03-01

    Formation of nacre (mother-of-pearl) is a biomineralization process of fundamental scientific as well as industrial importance. However, the dynamics of the formation process is still not understood. Here, we use scanning electron microscopy and high spatial resolution ion microprobe depth-profiling to image the full three-dimensional distribution of organic materials around individual tablets in the top-most layer of forming nacre in bivalves. Nacre formation proceeds by lateral, symmetric growth of individual tablets mediated by a growth-ring rich in organics, in which aragonite crystallizes from amorphous precursors. The pivotal role in nacre formation played by the growth-ring structure documented in this study adds further complexity to a highly dynamical biomineralization process.

  15. On spontaneous formation of current sheets: Untwisted magnetic fields

    SciTech Connect

    Bhattacharyya, R.; Low, B. C.; Smolarkiewicz, P. K.

    2010-11-15

    This is a study of the spontaneous formation of electric current sheets in an incompressible viscous fluid with perfect electrical conductivity, governed by the magnetohydrodynamic Navier-Stokes equations. Numerical solutions to two initial value problems are presented for a three-dimensional, periodic, untwisted magnetic field evolving, with no change in magnetic topology under the frozen-in condition and at characteristic fluid Reynolds numbers of the order of 500, from a nonequilibrium initial state with the fluid at rest. The evolution converts magnetic free energy into kinetic energy to be all dissipated away by viscosity so that the field settles into a minimum-energy, static equilibrium. The solutions demonstrate that, as a consequence of the frozen-in condition, current sheets must form during the evolution despite the geometric simplicity of the prescribed initial fields. In addition to the current sheets associated with magnetic neutral points and field reversal layers, other sheets not associated with such magnetic features are also in evidence. These current sheets form on magnetic flux surfaces. This property is used to achieve a high degree of the frozen-in condition in the simulations, by describing the magnetic field entirely in terms of the advection of its flux surfaces and integrating the resulting governing equations with a customized version of a general-purpose high-resolution (viz., nonoscillatory) hydrodynamical simulation code EULAG [J. M. Prusa et al., Comput. Fluids 37, 1193 (2008)]. Incompressibility imposes the additional global constraint that the flux surfaces must evolve with no change in the spatial volumes they enclose. In this approach, current sheet formation is demonstrated graphically by the progressive pressing together of suitably selected flux surfaces until their separation has diminished below the minimal resolved distance on a fixed grid. The frozen-in condition then fails in the simulation as the field reconnects through

  16. Metallopolymer-peptide conjugates: synthesis and self-assembly of polyferrocenylsilane graft and block copolymers containing a beta-sheet forming Gly-Ala-Gly-Ala tetrapeptide segment.

    PubMed

    Vandermeulen, Guido W M; Kim, Kyoung Taek; Wang, Zhuo; Manners, Ian

    2006-04-01

    We describe the synthesis and self-assembly of two beta-sheet forming metallopolymer-peptide conjugates. The ability of the oligotetrapeptide sequence Gly-Ala-Gly-Ala (GAGA) to form antiparallel beta-sheets was retained in PFS-b-AGAG (PFS = polyferrocenylsilane) and PFS-g-AGAG conjugates with block and graft architectures, respectively. In the solid state, DSC experiments suggest a phase separation between the peptide and PFS domains. In toluene, PFS-b-AGAG interestingly forms a fibrous network which consists of a core containing the self-assembled antiparallel beta-sheet peptide and a corona of organometallic PFS. The self-assembly of the peptide into antiparallel beta-sheets is the driving force for the fiber formation, whereas PFS prevents uncontrolled lateral aggregation of the fibers. The use of an oligopeptide to self-assemble an otherwise random coiled organometallic polymer may be a useful strategy to enhance nanostructure formation. In the cases described here, the conjugates may be used to create nanopatterned ceramics, and the redox properties of the resulting supramolecular aggregates are of significant interest. PMID:16602714

  17. Hydrophobic interactions and hydrogen bonds in β-sheet formation

    NASA Astrophysics Data System (ADS)

    Narayanan, Chitra; Dias, Cristiano L.

    2013-09-01

    In this study, we investigate interactions of extended conformations of homodimeric peptides made of small (glycine or alanine) and large hydrophobic (valine or leucine) sidechains using all-atom molecular dynamics simulations to decipher driving forces for β-sheet formation. We make use of a periodic boundary condition setup in which individual peptides are infinitely long and stretched. Dimers adopt β-sheet conformations at short interpeptide distances (ξ ˜ 0.5 nm) and at intermediate distances (˜0.8 nm), valine and leucine homodimers assume cross-β-like conformations with side chains interpenetrating each other. These two states are identified as minima in the potential of mean force. While the number of interpeptide hydrogen bonds increases with decreasing interpeptide distance, the total hydrogen bond number in the system does not change significantly, suggesting that formation of β-sheet structures from extended conformations is not driven by hydrogen bonds. This is supported by an increase in electrostatic energy at short interpeptide distances. A remarkable correlation between the volume of the system and the total electrostatic energy is observed, further reinforcing the idea that excluding water in proteins comes with an enthalpic penalty. We also discuss microscopic mechanisms accounting for β-sheet formation based on computed enthalpy and entropy and we show that they are different for peptides with small and large side chains.

  18. Thermally Induced Alpha-Helix to Beta-Sheet Transition in Regenerated Silk Fibers and Films

    SciTech Connect

    Drummy,L.; Phillips, D.; Stone, M.; Farmer, B.; Naik, R.

    2005-01-01

    The structure of thin films cast from regenerated solutions of Bombyx mori cocoon silk in hexafluoroisopropyl alcohol (HFIP) was studied by synchrotron X-ray diffraction during heating. A solid-state conformational transition from an alpha-helical structure to the well-known beta-sheet silk II structure occurred at a temperature of approximately 140 degrees C. The transition appeared to be homogeneous, as both phases do not coexist within the resolution of the current study. Modulated differential scanning calorimetry (DSC) of the films showed an endothermic melting peak followed by an exothermic crystallization peak, both occurring near 140 degrees C. Oriented fibers were also produced that displayed this helical molecular conformation. Subsequent heating above the structural transition temperature produced oriented beta-sheet fibers very similar in structure to B. mori cocoon fibers. Heat treatment of silk films at temperatures well below their degradation temperature offers a controllable route to materials with well-defined structures and mechanical behavior.

  19. Beta-hairpin formation in aqueous solution and in the presence of trifluoroethanol: a (1)H and (13)C nuclear magnetic resonance conformational study of designed peptides.

    PubMed

    Santiveri, Clara M; Pantoja-Uceda, David; Rico, Manuel; Jiménez, M Angeles

    2005-10-15

    In order to check our current knowledge on the principles involved in beta-hairpin formation, we have modified the sequence of a 3:5 beta-hairpin forming peptide with two different purposes, first to increase the stability of the formed 3:5 beta-hairpin, and second to convert the 3:5 beta-hairpin into a 2:2 beta-hairpin. The conformational behavior of the designed peptides was investigated in aqueous solution and in 30% trifluoroethanol (TFE) by analysis of the following nuclear magnetic resonance (NMR) parameters: nuclear Overhauser effect (NOE) data, and C(alpha)H, (13)C(alpha), and (13)C(beta) conformational shifts. From the differences in the ability to adopt beta-hairpin structures in these peptides, we have arrived to the following conclusions: (i) beta-Hairpin population increases with the statistical propensity of residues to occupy each turn position. (ii) The loop length, and in turn, the beta-hairpin type, can be modified as a function of the type of turn favored by the loop sequence. These two conclusions reinforce previous results about the importance of beta-turn sequence in beta-hairpin folding. (iii) Side-chain packing on each face of the beta-sheet may play a major role in beta-hairpin stability; hence simplified analysis in terms of isolated pair interactions and intrinsic beta-sheet propensities is insufficient. (iv) Contributions to beta-hairpin stability of turn and strand sequences are not completely independent. (v) The burial of hydrophobic surface upon beta-hairpin formation that, in turn, depends on side-chain packing also contributes to beta-hairpin stability. (vi) As previously observed, TFE stabilizes beta-hairpin structures, but the extent of the contribution of different factors to beta-hairpin formation is sometimes different in aqueous solution and in 30% TFE.

  20. Microscopic factors that control beta-sheet registry in amyloid fibrils formed by fragment 11-25 of amyloid beta peptide: insights from computer simulations.

    PubMed

    Negureanu, Lacramioara; Baumketner, Andrij

    2009-06-26

    Short fragments of amyloidogenic proteins are widely used as model systems in studies of amyloid formation. Fragment 11-25 of the amyloid beta protein involved in Alzheimer's disease (Abeta11-25) was recently shown to form amyloid fibrils composed of anti-parallel beta-sheets. Interestingly, fibrils grown under neutral and acidic conditions were seen to possess different registries of their inter-beta-strand hydrogen bonds. In an effort to explain the microscopic origin of this pH dependence, we studied Abeta11-25 fibrils using methods of theoretical modeling. Several structural models were built for fibrils at low and neutral pH levels and these were examined in short molecular dynamics simulations in explicit water. The models that displayed the lowest free energy, as estimated using an implicit solvent model, were selected as representative of the true fibrillar structure. It was shown that the registry of these models agrees well with the experimental results. At neutral pH, the main contribution to the free energy difference between the two registries comes from the electrostatic interactions. The charge group of the carboxy terminus makes a large contribution to these interactions and thus appears to have a critical role in determining the registry.

  1. Reduction of burn scar formation by halofuginone-eluting silicone gel sheets: a controlled study on nude mice.

    PubMed

    Zeplin, Philip H

    2012-03-01

    Burn scar formations can cause disfiguration and loss of dermal function. The purpose of this study was to examine whether application of modified silicone gel sheets with an antifibrotic drug halofuginone-eluting hybrid surface produce an effect on scar development. There were a total of 2 animal groups. The athymic nude mice (nu/nu) of both groups underwent transplantation of full-thickness human skin grafts onto their backs and setting of partial thickness burn injury. The status of local scar development was observed over a period of 3 months after the application of silicone gel sheets and also after application of surface-modified halofuginone-eluting silicone gel sheets. Subsequently, via real-time polymerase chain reaction, the cDNA levels from key mediators of scar formation (transforming growth factor beta, COL1A1, connective tissue growth factor, fibroblast growth factor 2, matrix metalloproteinase 2, matrix metalloproteinase 9) were established and statistically evaluated. In comparison with uncoated silicone gel sheets, the application of halofuginone-eluting silicone gel sheets lead to a significant difference in gene expression activity in scar tissue. Halofuginone-eluting hybrid surface silicone gel sheets significantly increase the antiscarring effect of adhesive silicone gel sheets by deceleration and downregulation of scar development by normalization of the expression activity.

  2. Blue color formation of cyanobacteria with beta-cyclocitral.

    PubMed

    Harada, Ken-Ichi; Ozaki, Keiko; Tsuzuki, Sayaka; Kato, Hajime; Hasegawa, Masateru; Kuroda, Emilia K; Arii, Suzue; Tsuji, Kiyomi

    2009-11-01

    Volatile compounds, such as beta-cyclocitral, geosmin, and 2-methylisoborneol, from cyanobacteria showed a lytic activity against cyanobacteria. Particularly, beta-cyclocitral caused an interesting color change in the culture broth from green to blue during the lysis process. In the present study, the lytic behavior of various cyanobacteria with beta-cyclocitral was investigated, and a mechanism for the blue color formation was developed. beta-Cyclocitral lysed both the laboratory strains of any genera and bloom samples including many species of cyanobacteria, and caused the characteristic color change from green to blue. beta-Cyclocitral provided a characteristic behavior, such that the absorption maxima of chlorophyll-a and beta-carotene disappeared, but that of phycocyanin still remained after 12 h, which indicated that beta-cyclocitral decomposed chlorophyll-a and beta-carotene rapidly, so that the inherent colors from the tolerant water-soluble pigments became observable in the cultured broth. This phenomenon was confirmed by another experiment using Phormidium (NIES-611), which showed a pink color derived from phycoerythrin. beta-Cyclocitral was more easily oxidized when compared with similar aldehyde compounds, so that the pH of the solution quickly decreased to 4.5. An oxidation product of beta-cyclocitral in water solution was isolated and identified as 2,6,6-trimethylcyclohexene-1-carboxylic acid. This study provides support that beta-cyclocitral derived from cyanobacteria plays an important role in the lysis of cyanobacteria and participates in the blue color formation under natural conditions.

  3. Design and biological activity of {beta}-sheet breaker peptide conjugates

    SciTech Connect

    Rocha, Sandra Cardoso, Isabel; Boerner, Hans; Pereira, Maria Carmo; Saraiva, Maria Joao; Coelho, Manuel

    2009-03-06

    The sequence LPFFD (iA{beta}{sub 5}) prevents amyloid-{beta} peptide (A{beta}) fibrillogenesis and neurotoxicity, hallmarks of Alzheimer's disease (AD), as previously demonstrated. In this study iA{beta}{sub 5} was covalently linked to poly(ethylene glycol) (PEG) and the activity of conjugates was assessed and compared to the activity of the peptide alone by in vitro studies. The conjugates were characterized by MALDI-TOF. Competition binding assays established that conjugates retained the ability to bind A{beta} with similar strength as iA{beta}{sub 5}. Transmission electron microscopy analysis showed that iA{beta}{sub 5} conjugates inhibited amyloid fibril formation, which is in agreement with binding properties observed for the conjugates towards A{beta}. The conjugates were also able to prevent amyloid-induced cell death, as evaluated by activation of caspase 3. These results demonstrated that the biological activity of iA{beta}{sub 5} is not affected by the pegylation process.

  4. Current sheet formation in a sheared magnetic field

    NASA Astrophysics Data System (ADS)

    Zhou, Yao; Huang, Yi-Min; Qin, Hong; Bhattacharjee, Amitava

    2015-11-01

    Recently a variational integrator for ideal magnetohydrodynamics in Lagrangian labeling has been developed using discrete exterior calculus. Its built-in frozen-in equation makes it optimal for studying current sheet formation. We use this scheme to study the Hahm-Kulsrud-Taylor problem, which considers the response of a 2D plasma magnetized by a sheared field under mirrored sinusoidal boundary perturbations. The equilibrium solutions are found to not converge with increasing spatial resolution, which suggests that there exists no smooth equilibrium that preserves the topology of the initial field exactly. Unlike previous studies that examine the current density output, we identify a singular current sheet from the converged part of the fluid mapping. This research was supported by the U.S. Department of Energy under Contract No. DE-AC02-09CH11466.

  5. CURRENT SHEETS FORMATION IN TANGLED CORONAL MAGNETIC FIELDS

    SciTech Connect

    Rappazzo, A. F.; Parker, E. N. E-mail: parker@oddjob.uchicago.edu

    2013-08-10

    We investigate the dynamical evolution of magnetic fields in closed regions of solar and stellar coronae. To understand under which conditions current sheets form, we examine dissipative and ideal reduced magnetohydrodynamic models in Cartesian geometry, where two magnetic field components are present: the strong guide field B{sub 0}, extended along the axial direction, and the dynamical orthogonal field b. Magnetic field lines thread the system along the axial direction that spans the length L and are line-tied at the top and bottom plates. The magnetic field b initially has only large scales, with its gradient (current) length scale of the order of l{sub b}. We identify the magnetic intensity threshold b/B{sub 0} {approx} l{sub b}/L. For values of b below this threshold, field-line tension inhibits the formation of current sheets, while above the threshold they form quickly on fast ideal timescales. In the ideal case, above the magnetic threshold, we show that current sheets thickness decreases in time until it becomes smaller than the grid resolution, with the analyticity strip width {delta} decreasing at least exponentially, after which the simulations become underresolved.

  6. The beta-sheet to alpha-helix transition of beta-lactoglobulin monitored in real time with a microfabricated IR mixer

    NASA Astrophysics Data System (ADS)

    Kauffmann, Ekkehard; Darton, Nick; Gerwert, Klaus; Austin, Robert

    2001-03-01

    The helix to sheet transition of proteins, a crucial step in amylogenic diseases, is investigated with a new diffusional IR mixer using time-resolved FTIR spectroscopy capable of 400 microsecond time resolution. We show that the beta to alpha transition of beta-lactoglobulin proceeds via a compact molten globule b-sheet intermediate with an unusually short lifetime of 7 ms. Because the protein does not have to unfold for the beta-sheet to alpha-helix transition the energy barrier seems to be unexpectedly low. The rough energy landscape of a protein includes not only the steep free energy funnel that guides the unfolded protein into its compact native state

  7. Factors contributing to decreased protein stability when aspartic acid residues are in {beta}-sheet regions.

    SciTech Connect

    Pokkuluri, P. R.; Cai, X.; Raffen, R.; Gu, M.; Stevens, F. J.; Schiffer, M.

    2002-07-01

    Asp residues are significantly under represented in {beta}-sheet regions of proteins, especially in the middle of {beta}-strands, as found by a number of studies using statistical, modeling, or experimental methods. To further understand the reasons for this under representation of Asp, we prepared and analyzed mutants of a {beta}-domain. Two Gln residues of the immunoglobulin light-chain variable domain (V{sub L}) of protein Len were replaced with Asp, and then the effects of these changes on protein stability and protein structure were studied. The replacement of Q38D, located at the end of a {beta}-strand, and that of Q89D, located in the middle of a {beta}-strand, reduced the stability of the parent immunoglobulin VL domain by 2.0 kcal/mol and 5.3 kcal/mol, respectively. Because the Q89D mutant of the wild-type V{sub L}-Len domain was too unstable to be expressed as a soluble protein, we prepared the Q89D mutant in a triple mutant background, V{sub L}-Len M4L/Y27dD/T94H, which was 4.2 kcal/mol more stable than the wild-type V{sub L}-Len domain. The structures of mutants V{sub L}-Len Q38D and V{sub L}-Len Q89D/M4L/Y27dD/T94H were determined by X-ray diffraction at 1.6 A resolution. We found no major perturbances in the structures of these QD mutant proteins relative to structures of the parent proteins. The observed stability changes have to be accounted for by cumulative effects of the following several factors: (1) by changes in main-chain dihedral angles and in side-chain rotomers, (2) by close contacts between some atoms, and, most significantly, (3) by the unfavorable electrostatic interactions between the Asp side chain and the carbonyls of the main chain. We show that the Asn side chain, which is of similar size but neutral, is less destabilizing. The detrimental effect of Asp within a {beta}-sheet of an immunoglobulin-type domain can have very serious consequences. A somatic mutation of a {beta}-strand residue to Asp could prevent the expression of the

  8. An exact collisionless equilibrium for the Force-Free Harris Sheet with low plasma beta

    SciTech Connect

    Allanson, O. Neukirch, T. Wilson, F. Troscheit, S.

    2015-10-15

    We present a first discussion and analysis of the physical properties of a new exact collisionless equilibrium for a one-dimensional nonlinear force-free magnetic field, namely, the force-free Harris sheet. The solution allows any value of the plasma beta, and crucially below unity, which previous nonlinear force-free collisionless equilibria could not. The distribution function involves infinite series of Hermite polynomials in the canonical momenta, of which the important mathematical properties of convergence and non-negativity have recently been proven. Plots of the distribution function are presented for the plasma beta modestly below unity, and we compare the shape of the distribution function in two of the velocity directions to a Maxwellian distribution.

  9. Moulin distribution and formation on the southwest Greenland ice sheet

    NASA Astrophysics Data System (ADS)

    Chu, V. W.; Smith, L. C.; Gleason, C. J.; Yang, K.; Poinar, K.; Joughin, I.; Pitcher, L. H.

    2015-12-01

    River moulins represent a significant connection between surface meltwater generated on the Greenland ice sheet and subglacial drainage networks, where increased meltwater can enhance ice sliding dynamics. In this study, a new high-resolution moulin map is created from WorldView-1/2 imagery acquired during the 2012 record melt year for a 12,500 km2 area near Russell Glacier in southwest Greenland. A total of 1,236 moulins are mapped and categorized as being located: in crevasse fields, along a single ice fracture, within drained lake basins, or having no visible formation mechanism. We find the presence of moulins up to 1787 m elevation, with 11% of moulins found above 1600 m elevation: higher than previously mapped moulins and where glaciological theory suggests few moulins should form. Our study observes moulins in both extensional and compressional ice flow regimes (28% of moulins are found in areas of high extensional strain rate >0.005 yr-1), suggesting that strain rates are not a strong indicator of the likelihood for moulin formation. Overall, moulin density tends to increase with higher bed elevation, thinner ice, lower surface slope, higher velocity, and higher strain rate. In sum, moulins are most common in crevassed, thinner ice near the ice sheet edge, but significant quantities also develop at high elevations. This indicates that future inland expansion of melting may create hydrologic connections between the surface and the bed at higher elevations than previously thought.

  10. sup 1 H NMR identification of a. beta. -sheet structure and description of folding topology in putidaredoxin

    SciTech Connect

    Pochapsky, T.C.; Ye, Xiao Mei )

    1991-04-23

    Putidaredoxin (Pdx), a 106-residue globular protein consisting of a single polypeptide chain and a (2Fe-2S) cluster, is the physiological reductant of P-450{sub cam}, which in turn catalyzes the monohydroxylation of camphor by molecular oxygen. No crystal structure has been obtained for Pdx or for any closely homologous protein. The application of two-dimensional {sup 1}H NMR methods to the problem of structure determination in Pdx is reported. A {beta}-sheet consisting of five short strands and one {beta}-turn has been identified from distinctive nuclear Overhauser effect patterns. All of the backbone resonances and a majority of the side-chain resonances corresponding to protons in the {beta}-sheet have been assigned sequence specifically. The sheet contains one parallel and three antiparallel strand orientations. Hydrophobic side chains in the {beta}-sheet face primarily toward the protein interior, except for a group of three valine side chains that are apparently solvent exposed. The potential significance of this hydrophobic patch in terms of biological activity is discussed. The folding topology, as determined by the constraints of the {beta}-sheet, is compared with that of other (2Fe-2S) proteins for which folding topologies are known.

  11. Microphase Separation Controlled beta-Sheet Crystallization Kinetics in Fibrous Proteins

    SciTech Connect

    Hu, X.; Lu, Q; Kaplan, D; Cebe, P

    2009-01-01

    Silk is a naturally occurring fibrous protein with a multiblock chain architecture. As such, it has many similarities with synthetic block copolymers, including the possibility for e-sheet crystallization restricted within the crystallizable blocks. The mechanism of isothermal crystallization kinetics of e-sheet crystals in silk multiblock fibrous proteins is reported in this study. Kinetics theories, such as Avrami analysis which was established for studies of synthetic polymer crystal growth, are for the first time extended to investigate protein self-assembly in e-sheet rich Bombyx mori silk fibroin samples, using time-resolved Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and synchrotron real-time wide-angle X-ray scattering (WAXS). The Avrami exponent, n, was close to 2 for all methods and crystallization temperatures, indicating formation of e-sheet crystals in silk proteins is different from the 3-D spherulitic crystal growth found in synthetic polymers. Observations by scanning electron microscopy support the view that the protein structures vary during the different stages of crystal growth, and show a microphase separation pattern after chymotrypsin enzyme biodegradation. We present a model to explain the crystallization of the multiblock silk fibroin protein, by analogy to block copolymers: crystallization of e-sheets occurs under conditions of geometrical restriction caused by phase separation of the crystallizable and uncrystallizable blocks. This crystallization model could be widely applicable in other proteins with multiblock (i.e., crystallizable and noncrystallizable) domains.

  12. Designing biomaterials exploiting beta-sheet forming peptides self-assembly

    NASA Astrophysics Data System (ADS)

    Saiani, Alberto

    2013-03-01

    The use of non-covalent self-assembly to construct materials has become a prominent strategy in material science offering practical routes for the construction of increasingly functional materials for a variety of applications ranging from electronic to biotechnology. A variety of molecular building blocks can be used for this purpose, one such block that has attracted considerable attention are de-novo designed peptides. The library of 20 natural amino acids offers the ability to play with the intrinsic properties of the peptide such as structure, hydrophobicity, charge and functionality allowing the design of materials with a wide range of properties. The beta-sheet motif is of particular interest as short peptides can be designed to form beta-sheet rich fibres that entangle and consequently form hydrogels. These hydrogels can be further functionalised using specific biological signals or drugs by synthesising functionalised peptides that are incorporated into the hydrogel network during the self-assembling process. This functionalisation approach is very attractive has it does not require any chemistry avoiding therefore the use of additional potentially toxic chemicals. It also offers the possibility to introduce multiple functionalities in a straightforward fashion. The hydrogels can also be made responsive through the use of enzymatic catalysis and/or conjugation with responsive polymers. In this presentation we will discuss the design opportunities offered by these peptides to create new functional biomaterials.

  13. Strength limit of entropic elasticity in beta-sheet protein domains

    NASA Astrophysics Data System (ADS)

    Keten, Sinan; Buehler, Markus J.

    2008-12-01

    Elasticity and strength of individual beta-sheet protein domains govern key biological functions and the mechanical properties of biopolymers including spider silk, amyloids, and muscle fibers. The worm-like-chain (WLC) model is commonly used to describe the entropic elasticity of polypeptides and other biomolecules. However, force spectroscopy experiments have shown pronounced deviations from the ideal WLC behavior, leading to controversial views about the appropriate elastic description of proteins at nanoscale. Here we report a simple model that explains the physical mechanism that leads to the breakdown of the WLC idealization in experiments by using only two generic parameters of the protein domain, the H-bond energy and the protein backbone’s persistence length. We show that a rupture initiation condition characterized by the free energy release rate of H-bonds characterizes the limit of WLC entropic elasticity of beta-sheet protein domains and the onset of rupture. Our findings reveal that strength and elasticity are coupled and cannot be treated separately. The predictions of the model are compared with atomic force microscopy experiments of protein rupture.

  14. Helix versus sheet formation in a small peptide

    NASA Astrophysics Data System (ADS)

    Peng, Yong; Hansmann, Ulrich H.

    2003-10-01

    Segments with the amino acid sequence EKAYLRT (glutamine-lysine-alanine-tyrosine-leucine-arginine-threonine) appear in naturally occurring proteins both in α-helices and β-sheets. For this reason, we have used this peptide to study how secondary structure formation in proteins depends on the local environment. Our data rely on multicanonical Monte Carlo simulations where the interactions among all atoms are taken into account. Results in gas phase are compared with that in an implicit solvent. We find that both the solvated molecule and EKAYLRT in gas phase form an α-helix when not interacting with other molecules. However, in the vicinity of a β-strand, the peptide forms a β-strand. Because of this change in secondary structure our peptide may provide a simple model for the α→β transition that is supposedly related to the outbreak of prion diseases and similar illnesses.

  15. Reversible Hydrogel–Solution System of Silk with High Beta-Sheet Content

    PubMed Central

    2015-01-01

    Silkworm silk has been widely used as a textile fiber, as biomaterials and in optically functional materials due to its extraordinary properties. The β-sheet-rich natural nanofiber units of about 10–50 nm in diameter are often considered the origin of these properties, yet it remains unclear how silk self-assembles into these hierarchical structures. A new system composed of β-sheet-rich silk nanofibers about 10–20 nm in diameter is reported here, where these nanofibers formed into “flowing hydrogels” at 0.5–2% solutions and could be transformed back into the solution state at lower concentrations, even with a high β-sheet content. This is in contrast with other silk processed materials, where significant β-sheet content negates reversibility between solution and solid states. These fibers are formed by regulating the self-assembly process of silk in aqueous solution, which changes the distribution of negative charges while still supporting β-sheet formation in the structures. Mechanistically, there appears to be a shift toward negative charges along the outside of the silk nanofibers in our present study, resulting in a higher zeta potential (above −50 mV) than previous silk materials which tend to be below −30 mV. The higher negative charge on silk nanofibers resulted in electrostatic repulsion strong enough to negate further assembly of the nanofibers. Changing silk concentration changed the balance between hydrophobic interactions and electrostatic repulsion of β-sheet-rich silk nanofibers, resulting in reversible hydrogel–solution transitions. Furthermore, the silk nanofibers could be disassembled into shorter fibers and even nanoparticles upon ultrasonic treatment following the transition from hydrogel to solution due to the increased dispersion of hydrophobic smaller particles, without the loss of β-sheet content, and with retention of the ability to transition between hydrogel and solution states through reversion to longer nanofibers

  16. Reversible hydrogel-solution system of silk with high beta-sheet content.

    PubMed

    Bai, Shumeng; Zhang, Xiuli; Lu, Qiang; Sheng, Weiqin; Liu, Lijie; Dong, Boju; Kaplan, David L; Zhu, Hesun

    2014-08-11

    Silkworm silk has been widely used as a textile fiber, as biomaterials and in optically functional materials due to its extraordinary properties. The β-sheet-rich natural nanofiber units of about 10-50 nm in diameter are often considered the origin of these properties, yet it remains unclear how silk self-assembles into these hierarchical structures. A new system composed of β-sheet-rich silk nanofibers about 10-20 nm in diameter is reported here, where these nanofibers formed into "flowing hydrogels" at 0.5-2% solutions and could be transformed back into the solution state at lower concentrations, even with a high β-sheet content. This is in contrast with other silk processed materials, where significant β-sheet content negates reversibility between solution and solid states. These fibers are formed by regulating the self-assembly process of silk in aqueous solution, which changes the distribution of negative charges while still supporting β-sheet formation in the structures. Mechanistically, there appears to be a shift toward negative charges along the outside of the silk nanofibers in our present study, resulting in a higher zeta potential (above -50 mV) than previous silk materials which tend to be below -30 mV. The higher negative charge on silk nanofibers resulted in electrostatic repulsion strong enough to negate further assembly of the nanofibers. Changing silk concentration changed the balance between hydrophobic interactions and electrostatic repulsion of β-sheet-rich silk nanofibers, resulting in reversible hydrogel-solution transitions. Furthermore, the silk nanofibers could be disassembled into shorter fibers and even nanoparticles upon ultrasonic treatment following the transition from hydrogel to solution due to the increased dispersion of hydrophobic smaller particles, without the loss of β-sheet content, and with retention of the ability to transition between hydrogel and solution states through reversion to longer nanofibers during self

  17. Amide-I and -II vibrations of the cyclic beta-sheet model peptide gramicidin S in the gas phase.

    PubMed

    Kupser, Peter; Pagel, Kevin; Oomens, Jos; Polfer, Nick; Koksch, Beate; Meijer, Gerard; von Helden, Gert

    2010-02-17

    In the condensed phase, the peptide gramicidin S is often considered as a model system for a beta-sheet structure. Here, we investigate gramicidin S free of any influences of the environment by measuring the mid-IR spectra of doubly protonated (deuterated) gramicidin S in the gas phase. In the amide I (i.e., C=O stretch) region, the spectra show a broad split peak between 1580 and 1720 cm(-1). To deduce structural information, the conformational space has been searched using molecular dynamics methods and several structural candidates have been further investigated at the density functional level. The calculations show the importance of the interactions of the charged side-chains with the backbone, which is responsible for the lower frequency part of the amide I peak. When this interaction is inhibited via complexation with two 18-crown-6 molecules, the amide I peak narrows and shows two maxima at 1653 and 1680 cm(-1). A comparison to calculations shows that for this complexed ion, four C=O groups are in an antiparallel beta-sheet arrangement. Surprisingly, an analysis of the calculated spectra shows that these beta-sheet C=O groups give rise to the vibrations near 1680 cm(-1). This is in sharp contrast to expectations based on values for the condensed phase, where resonances of beta-sheet sections are thought to occur near 1630 cm(-1). The difference between those values might be caused by interactions with the environment, as the condensed phase value is mostly deduced for beta-sheet sections that are embedded in larger proteins, that interact strongly with solvent or that are part of partially aggregated species.

  18. Hybrid modeling of the formation and structure of thin current sheets in the magnetotail

    SciTech Connect

    Hesse, M.; Winske, D.; Birn, J.

    1996-07-01

    Hybrid simulations are used to investigate the formation of a thin current sheet inside the plasma sheet of a magnetotail-like configuration. The initial equilibrium is subjected to a driving electric field qualitatively similar to what would be expected from solar wind driving. As a result, we find the formation of a raw current sheet, with a thickness of approximately the ion inertial length. The current density inside the current sheet region is supplied largely by the electrons. Ion acceleration in the cross-tail direction is absent due since the driving electric field fails to penetrate into the equatorial region.

  19. PB1-F2 influenza A virus protein adopts a beta-sheet conformation and forms amyloid fibers in membrane environments.

    PubMed

    Chevalier, Christophe; Al Bazzal, Ali; Vidic, Jasmina; Février, Vincent; Bourdieu, Christiane; Bouguyon, Edwige; Le Goffic, Ronan; Vautherot, Jean-François; Bernard, Julie; Moudjou, Mohammed; Noinville, Sylvie; Chich, Jean-François; Da Costa, Bruno; Rezaei, Human; Delmas, Bernard

    2010-04-23

    The influenza A virus PB1-F2 protein, encoded by an alternative reading frame in the PB1 polymerase gene, displays a high sequence polymorphism and is reported to contribute to viral pathogenesis in a sequence-specific manner. To gain insights into the functions of PB1-F2, the molecular structure of several PB1-F2 variants produced in Escherichia coli was investigated in different environments. Circular dichroism spectroscopy shows that all variants have a random coil secondary structure in aqueous solution. When incubated in trifluoroethanol polar solvent, all PB1-F2 variants adopt an alpha-helix-rich structure, whereas incubated in acetonitrile, a solvent of medium polarity mimicking the membrane environment, they display beta-sheet secondary structures. Incubated with asolectin liposomes and SDS micelles, PB1-F2 variants also acquire a beta-sheet structure. Dynamic light scattering revealed that the presence of beta-sheets is correlated with an oligomerization/aggregation of PB1-F2. Electron microscopy showed that PB1-F2 forms amorphous aggregates in acetonitrile. In contrast, at low concentrations of SDS, PB1-F2 variants exhibited various abilities to form fibers that were evidenced as amyloid fibers in a thioflavin T assay. Using a recombinant virus and its PB1-F2 knock-out mutant, we show that PB1-F2 also forms amyloid structures in infected cells. Functional membrane permeabilization assays revealed that the PB1-F2 variants can perforate membranes at nanomolar concentrations but with activities found to be sequence-dependent and not obviously correlated with their differential ability to form amyloid fibers. All of these observations suggest that PB1-F2 could be involved in physiological processes through different pathways, permeabilization of cellular membranes, and amyloid fiber formation.

  20. Structure of a Nudix protein from Pyrobaculum aerophilum reveals a dimer with two intersubunit beta-sheets.

    PubMed

    Wang, Shuishu; Mura, Cameron; Sawaya, Michael R; Cascio, Duilio; Eisenberg, David

    2002-04-01

    Nudix proteins, formerly called MutT homolog proteins, are a large family of proteins that play an important role in reducing the accumulation of potentially toxic compounds inside the cell. They hydrolyze a wide variety of substrates that are mainly composed of a nucleoside diphosphate linked to some other moiety X and thus are called Nudix hydrolases. Here, the crystal structure of a Nudix hydrolase from the hyperthermophilic archaeon Pyrobaculum aerophilum is reported. The structure was determined by the single-wavelength anomalous scattering method with data collected at the peak anomalous wavelength of an iridium-derivatized crystal. It reveals an extensive dimer interface, with each subunit contributing two strands to the beta-sheet of the other subunit. Individual subunits consist of a mixed highly twisted and curved beta-sheet of 11 beta-strands and two alpha-helices, forming an alpha-beta-alpha sandwich. The conserved Nudix box signature motif, which contains the essential catalytic residues, is located at the first alpha-helix and the beta-strand and loop preceding it. The unusually short connections between secondary-structural elements, together with the dimer form of the structure, are likely to contribute to the thermostability of the P. aerophilum Nudix protein.

  1. Membrane Pore Formation by Amyloid beta (25-35) Peptide

    NASA Astrophysics Data System (ADS)

    Kandel, Nabin; Tatulian, Suren

    Amyloid (A β) peptide contributes to Alzheimer's disease by a yet unidentified mechanism. One of the possible mechanisms of A β toxicity is formation of pores in cellular membranes. We have characterized the formation of pores in phospholipid membranes by the Aβ25 - 35 peptide (GSNKGAIIGLM) using fluorescence, Fourier transform infrared spectroscopy (FTIR) and circular dichroism (CD) techniques. CD and FTIR identified formation of β-sheet structure upon incubation of the peptide in aqueous buffer for 2 hours. Unilamellar vesicles composed of a zwitterionic lipid, 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC), and 70 % POPC plus 30 % of an acidic lipid, 1-palmitoyl-2-oleoyl-phosphatidylglycerol (POPG), are made in 30 mM CaCl2. Quin-2, a fluorophore that displays increased fluorescence upon Ca2+ binding, is added to the vesicles externally. Peptide addition results in increased Quin-2 fluorescence, which is interpreted by binding of the peptide to the vesicles, pore formation, and Ca2+ leakage. The positive and negative control measurements involve addition of a detergent, Triton X-100, which causes vesicle rupture and release of total calcium, and blank buffer, respectively.

  2. Collective oscillations and the linear and two-dimensional infrared spectra of inhomogeneous beta-sheets.

    PubMed

    Dijkstra, Arend G; Knoester, Jasper

    2005-05-19

    We numerically calculate the collective amide I oscillations and the associated linear and two-dimensional infrared (2DIR) spectra for model antiparallel beta-sheets and study the effect of inhomogeneity. To visualize the collective vibrational exciton states, a new method is introduced, which proves very useful in classifying the optically dominant states with respect to their symmetry properties and phase relations, even in the absence of exact symmetries. We find that energy (diagonal) and interaction (off-diagonal) disorder may have profoundly different effects on the main peaks in the linear spectrum. We also show that in the 2DIR spectra energy disorder leads to diagonal stretching of the diagonal peaks, while the cross-peaks are typically stretched more horizontally. This offers an explanation for the recently observed overall Z-shape in experimental spectra. Finally, we find that the anharmonic splitting between associated positive and negative features in the 2DIR spectra scales inversely proportionally with the exciton delocalization size imposed by the disorder, thus offering a spectroscopic ruler for this size. PMID:16852179

  3. Deuterium exchange of alpha-helices and beta-sheets as monitored by electrospray ionization mass spectrometry.

    PubMed Central

    Wagner, D. S.; Melton, L. G.; Yan, Y.; Erickson, B. W.; Anderegg, R. J.

    1994-01-01

    Deuterium exchange was monitored by electrospray ionization mass spectrometry (ESI-MS) to study the slowly exchanging (hydrogen bonded) peptide hydrogens of several alpha-helical peptides and beta-sheet proteins. Polypeptides were synthetically engineered to have mainly disordered, alpha-helical, or beta-sheet structure. For 3 isomeric 31-residue alpha-helical peptides, the number of slowly exchanging hydrogens as measured by ESI-MS in 50% CF3CD2OD (pD 9.5) provided estimates of their alpha-helicities (26%, 40%, 94%) that agreed well with the values (17%, 34%, 98%) measured by circular dichroic spectroscopy in the same nondeuterated solvent. For 3 betabellins containing a pair of beta-sheets and a related disordered peptide, their order of structural stability (12D > 12S > 14D > 14S) shown by their deuterium exchange rates in 10% CD3OD/0.5% CD3CO2D (pD 3.8) as measured by ESI-MS was the same as their order of structural stability to unfolding with increasing temperature or guanidinium chloride concentration as measured by circular dichroic spectroscopy in water. Compared to monitoring deuterium exchange by proton NMR spectrometry, monitoring deuterium exchange by ESI-MS requires much less sample (1-50 micrograms), much shorter analysis time (10-90 min), and no chemical quenching of the exchange reaction. PMID:7987225

  4. A novel mode of DNA recognition by a beta-sheet revealed by the solution structure of the GCC-box binding domain in complex with DNA.

    PubMed Central

    Allen, M D; Yamasaki, K; Ohme-Takagi, M; Tateno, M; Suzuki, M

    1998-01-01

    The 3D solution structure of the GCC-box binding domain of a protein from Arabidopsis thaliana in complex with its target DNA fragment has been determined by heteronuclear multidimensional NMR in combination with simulated annealing and restrained molecular dynamic calculation. The domain consists of a three-stranded anti-parallel beta-sheet and an alpha-helix packed approximately parallel to the beta-sheet. Arginine and tryptophan residues in the beta-sheet are identified to contact eight of the nine consecutive base pairs in the major groove, and at the same time bind to the sugar phosphate backbones. The target DNA bends slightly at the central CG step, thereby allowing the DNA to follow the curvature of the beta-sheet. PMID:9736626

  5. Non-Traditional Answer-Sheet Format: Solution or Problem?

    ERIC Educational Resources Information Center

    Ferguson, William F.

    College undergraduates (n=38) were administered identical multiple choice tests with randomly presented answer-sheets numbered either vertically or horizontally. Of the originally-scheduled four tests during the semester, tests one and three were retested with entirely different test questions, also multiple choice, resulting in scores from tests,…

  6. The crystal structure of human glycosylation-inhibiting factor is a trimeric barrel with three 6-stranded beta-sheets.

    PubMed Central

    Kato, Y; Muto, T; Tomura, T; Tsumura, H; Watarai, H; Mikayama, T; Ishizaka, K; Kuroki, R

    1996-01-01

    Glycosylation-inhibiting factor (GIF) is a cytokine that is involved in the regulation of IgE synthesis. The crystal structure of recombinant human GIF was determined by the multiple isomorphous replacement method. The structure was refined to an R factor of 0.168 at 1.9 angstrom resolution. The overall structure is seen to consist of three interconnected subunits forming a barrel with three 6-stranded beta-sheets on the inside and six alpha-helices on the outside. There is a 5-angstrom-diameter "hole" through the middle of the barrel. The barrel structure of GIF in part resembles other "trefoil" cytokines such as interleukin 1 and fibroblast growth factor. Each subunit has a new class of alpha + beta sandwich structure consisting of two beta-alpha-beta motifs. These beta-alpha-beta motifs are related by a pseudo-twofold axis and resemble both interleukin 8 and the peptide binding domain of major histocompatibility complex protein, although the topology of the polypeptide chain is quite different. Images Fig. 1 Fig. 3 PMID:8610159

  7. Current Sheet Formation in a Conical Theta Pinch Faraday Accelerator with Radio-frequency Assisted Discharge

    NASA Technical Reports Server (NTRS)

    Polzin, Kurt A.; Hallock, Ashley K.; Choueiri, Edgar Y.

    2008-01-01

    Data from an inductive conical theta pinch accelerator are presented to gain insight into the process of inductive current sheet formation in the presence of a preionized background gas produced by a steady-state RF-discharge. The presence of a preionized plasma has been previously shown to allow for current sheet formation at lower discharge voltages and energies than those found in other pulsed inductive accelerator concepts, leading to greater accelerator efficiencies at lower power levels. Time-resolved magnetic probe measurements are obtained for different background pressures and pulse energies to characterize the effects of these parameters on current sheet formation. Indices are defined that describe time-resolved current sheet characteristics, such as the total current owing in the current sheet, the time-integrated total current ('strength'), and current sheet velocity. It is found that for a given electric field strength, maximums in total current, strength, and velocity occur for one particular background pressure. At other pressures, these current sheet indices are considerably smaller. The trends observed in these indices are explained in terms of the principles behind Townsend breakdown that lead to a dependence on the ratio of the electric field to the background pressure. Time-integrated photographic data are also obtained at the same experimental conditions, and qualitatively they compare quite favorably with the time-resolved magnetic field data.

  8. The peculiarities of formation of thin current sheet in the Earth's magnetotail

    NASA Astrophysics Data System (ADS)

    Kropotkin, Alexey; Artemyev, Anton; Malova, Helmi; Domrin, Vladimir

    We investigate the process of self-consistent thinning of magnetotail current sheet in the presence of the evolving magnetic field normal component Bz, which usually decreases during the substorm growth phase. Using PIC codes to describe plasma processes with ions becoming demagnetized and electrons being considered as the cold neutralizing background, we show that the appearance of the self-consistent electric field component inside CS can lead to the current sheet thinning and to the appearance of an extremely thin current sheet with thickness close to the ion gyroradius. Due to particle [ExB] drift during the current sheet evolution, the enhanced trapping of ions near the current sheet central plane takes place. It is shown that the density of quasi-trapped particles around current sheet at the final stage depends on both the value of the initial magnetic field normal component Bz, and the speed of the Bz decrease. If the initial magnetic field normal component is less than about 0.14 of the tangential field at the edges, the trapped plasma density near the current sheet is small. As a result, the above mentioned extremely thin current sheet is formed. In the opposite case, when the initial normal component related to the tangential field is larger than 0.14, the density of trapped particles is much higher, which produces effective thickening of the current sheet. In both cases transient (Speiser) ions are the main current carriers, but in the second case local diamagnetic currents of the trapped plasma perturb the сurrent sheet profile making it thicker. Also trapped particles can be responsible for intense negative currents at the current sheet edges. During the Bz decrease, an additional effect of ion polarization drifts in the Y direction can compete with these negative diamagnetic fields of quasi-trapped ions. Therefore the ion dynamics is probably the general mechanism which contributes to the formation of thin current sheet and its fine structure.

  9. [Neutralization of static electricity charged on running vinyl chloride sheet by the use of soft beta-ray sources (author's transl)].

    PubMed

    Itakura, K; Wada, N

    1978-04-01

    The feasibility of 147Pm and 3H beta-ray sources as static eliminator was experimentally investigated. A sheet of vinyl chloride of 0.1 mm in thickness was used as an example of electrified materials. Its surface charge densities before and after beta-ray neutralization were measured as the function of electrostatic charge changing the speed of the sheet and the distance between the beta-ray source and the sheet. With a 147Pm beta-ray source of 200mCi in effective activity, almost complete neutralization was found for the sheet with the charge density less than 6 X 10(-6) C/m2 running at the speed of 0.18 m/s. In the case of the running speed of 0.5 m/s frequently used in industry, the electrostatic charge below 3 X 10(6) C/m2, where corona discharger is not so effective, was also perfectly eliminated. It was found that the optimal distance between the beta-ray source and the sheet was 10 cm in the case of 147Pm. The use of 3H beta-ray source of 1 Ci was not satisfactory. These results demonstrate that 147 Pm beta-ray source operates most efficiently as static eliminator when the charge density of material and/or its moving speed is not high.

  10. Spontaneous formation of electric current sheets and the origin of solar flares

    NASA Technical Reports Server (NTRS)

    Low, B. C.; Wolfson, R.

    1988-01-01

    It is demonstrated that the continuous boundary motion of a sheared magnetic field in a tenuous plasma with an infinite electrical conductivity can induce the formation of multiple electric current sheets in the interior plasma. In response to specific footpoint displacements, the quadrupolar magnetic field considered is shown to require the formation of multiple electric current sheets as it achieves a force-free state. Some of the current sheets are found to be of finite length, running along separatrix lines of force which separate lobes of magnetic flux. It is suggested that current sheets in the form of infinitely thin magnetic shear layers may be unstable to resistive tearing, a process which may have application to solar flares.

  11. Formation and Properties of Magnetic Island Plasmoids in Large-Scale Current Sheets During CME Eruptions

    NASA Astrophysics Data System (ADS)

    Lynch, Benjamin J.; Edmondson, Justin K

    2014-06-01

    We present the continued analysis of the high-resolution 2.5D MHD simulations of sympathetic magnetic breakout eruptions from a pseudostreamer source region. We examine the generation of X- and O-type null points during the current sheet tearing and their evolution as reconnection progresses. There are three large-scale current sheets that we investigate in detail over the course of the simulation. We examine the properties of reconnection occurring within these current sheets including evolution of the current sheet lengths, Lundquist number, and reconnection rates. We also quantify the statistical and spectral properties of the fluctuations in the current sheets resulting from the resistive tearing and magnetic island plasmoid formation including the distribution of magnetic island width, flux content, and mass. We show that the temporal evolution of the spectral index of the magnetic energy density in our current sheets appears to reflect the transition from the linear to non-linear phase of the instability. Our results are in excellent agreement with recent dedicated reconnection simulations even though our current sheets’ formation, growth, and dynamics are both dictated by and in turn, govern the global evolution of sequential, sympathetic CME eruptions.

  12. The solubilization of model Alzheimer tangles: reversing the beta-sheet conformation induced by aluminum with silicates.

    PubMed Central

    Fasman, G D; Moore, C D

    1994-01-01

    Neurofibrillary tangles are one of two lesions found in the brain of Alzheimer disease victims. With synthetic peptide fragments of human neurofilament NF-M17 (Glu-Glu-Lys-Gly-Lys-Ser-Pro- Val-Pro-Lys-Ser-Pro-Val-Glu-Glu-Lys-Gly, phosphorylated and unphosphorylated), CD studies were done to examine the effect of sodium orthosilicate on the conformational state produced by Al3+ on fragments of neuronal proteins. Previous studies had shown a conformational transition from alpha-helix and random to beta-pleated sheet upon addition of Al3+ to both phosphorylated and unphosphorylated peptides. If sufficient quantities of Al3+ are added, the peptide precipitates from solution. The ability to reverse or slow the progression of aggregation was examined. Al3+ binding was reversed with 1-2 molar equivalents of sodium orthosilicate (with respect to Al3+), altering the conformation from beta-sheet to random coil and resulting in a CD spectrum similar to that of the initial peptide. The tight binding of the SiO4(4-) with the Al3+ provides the mechanism for this transition. These results provide additional information toward understanding the role of aluminum in the Alzheimer diseased brain and suggest the investigation of the possible use of silicates as a therapeutic agent. PMID:7972040

  13. Amyloids of shuffled prion domains that form prions have a parallel in-register beta-sheet structure.

    PubMed

    Shewmaker, Frank; Ross, Eric D; Tycko, Robert; Wickner, Reed B

    2008-04-01

    The [URE3] and [PSI (+)] prions of Saccharomyces cerevisiae are self-propagating amyloid forms of Ure2p and Sup35p, respectively. The Q/N-rich N-terminal domains of each protein are necessary and sufficient for the prion properties of these proteins, forming in each case their amyloid cores. Surprisingly, shuffling either prion domain, leaving amino acid content unchanged, does not abrogate the ability of the proteins to become prions. The discovery that the amino acid composition of a polypeptide, not the specific sequence order, determines prion capability seems contrary to the standard folding paradigm that amino acid sequence determines protein fold. The shuffleability of a prion domain further suggests that the beta-sheet structure is of the parallel in-register type, and indeed, the normal Ure2 and Sup35 prion domains have such a structure. We demonstrate that two shuffled Ure2 prion domains capable of being prions form parallel in-register beta-sheet structures, and our data indicate the same conclusion for a single shuffled Sup35 prion domain. This result confirms our inference that shuffleability indicates parallel in-register structure.

  14. Interaction of self-assembling beta-sheet peptides with phospholipid monolayers: the role of aggregation state, polarity, charge and applied field.

    PubMed

    Protopapa, Elisabeth; Maude, Steven; Aggeli, Amalia; Nelson, Andrew

    2009-03-01

    Studies of beta-sheet peptide/phospholipid interactions are important for an understanding of the folding of beta-sheet-rich membrane proteins and the action of antimicrobial and toxic peptides. Further, self-assembling peptides have numerous applications in medicine and therefore an insight is required into the relation between peptide molecular structure and biomembrane activity. We previously developed one of the simplest known model peptide systems which, above a critical concentration (c*) in solution, undergoes nucleated one-dimensional self-assembly from a monomeric random coil into a hierarchy of well defined beta-sheet structures. Here we examine the effects of peptide aggregation, polarity, charge, and applied field on peptide interactions with dioleoyl phosphatidylcholine (DOPC) monolayers using electrochemical techniques. The interactions of six systematically altered 11 residue beta-sheet tape-forming peptides were investigated. The following findings with respect to 11 residue beta-sheet peptide-DOPC interaction arose from the study: (i) The solution monomer peptide species is the monolayer active moeity. (ii) Amphiphilic peptides are more monolayer active than polar peptides in the absence of applied electric field. (iii) Positive charge on amphiphilic peptides facilitates monolayer interaction in the absence of applied electric field. (iv) Negative applied electric field facilitates monolayer interaction with positively charged amphiphilic and polar peptides. (v) Neutral amphiphilic peptides permeabilize DOPC layers to ions to the greatest extent. (vi) The beta-sheet tape forming peptides are shown to be significantly less monolayer disruptive than antimicrobial peptides. These conclusions will greatly contribute to the rational design of new peptide-based biomaterials and biosensors.

  15. The palladium assisted transfer reduction of. alpha. ,. beta. -unsaturated nitroalkenes to oximes using ammonium formate

    SciTech Connect

    Kabalka, G.W.; Pace, R.D.; Wadgaonkar, P.P. )

    1990-01-01

    {alpha},{beta}-Unsaturated nitroalkenes are readily reduced to the corresponding oximes in good yields using ammonium formate in the presence of palladium. The reactions occur rapidly at room temperature in a solvent system of methanol and tetrahydrofuran.

  16. EGCG Inhibited Lipofuscin Formation Based on Intercepting Amyloidogenic β-Sheet-Rich Structure Conversion

    PubMed Central

    Cai, Shuxian; Yang, Heng; Zeng, Kewu; Zhang, Jing; Zhong, Ni; Wang, Yingzi; Ye, Jing; Tu, Pengfei; Liu, Zhonghua

    2016-01-01

    Background Lipofuscin (LF) is formed during lipid peroxidation and sugar glycosylation by carbonyl-amino crosslinks with biomacrolecules, and accumulates slowly within postmitotic cells. The environmental pollution, modern dietary culture and lifestyle changes have been found to be the major sources of reactive carbonyl compounds in vivo. Irreversible carbonyl-amino crosslinks induced by carbonyl stress are essentially toxiferous for aging-related functional losses in modern society. Results show that (-)-epigallocatechin gallate (EGCG), the main polyphenol in green tea, can neutralize the carbonyl-amino cross-linking reaction and inhibit LF formation, but the underlying mechanism is unknown. Methods and Results We explored the mechanism of the neutralization process from protein, cell, and animal levels using spectrofluorometry, infrared spectroscopy, conformation antibodies, and electron microscopy. LF demonstrated an amyloidogenic β-sheet-rich with antiparallel structure, which accelerated the carbonyl-amino crosslinks formation and disrupted proteolysis in both PC12 cells and D-galactose (D-gal)-induced brain aging mice models. Additionally, EGCG effectively inhibited the formation of the amyloidogenic β-sheet-rich structure of LF, and prevented its conversion into toxic and on-pathway aggregation intermediates, thereby cutting off the carbonyl-amino crosslinks. Conclusions Our study indicated that the amyloidogenic β-sheet structure of LF may be the core driving force for carbonyl-amino crosslinks further formation, which mediates the formation of amyloid fibrils from native state of biomacrolecules. That EGCG exhibits anti-amyloidogenic β-sheet-rich structure properties to prevent the LF formation represents a novel strategy to impede the development of degenerative processes caused by ageing or stress-induced premature senescence in modern environments. PMID:27030967

  17. Formation of beta-lactamase in Bacteroides fragilis: cell-bound and extracellular activity.

    PubMed

    Olsson, B; Nord, C E; Wadström, T

    1976-05-01

    Nine strains of Bacteroides fragilis were cultivated in stirred fermentors and tested for their ability to produce beta-lactamase. There was a correlation between formation of beta-lactamase and high values of the minimal inhibitory concentration against beta-lactam antibiotics. B. fragilis strain B70 was used for optimizing the production of beta-lactamase. The highest bacterial yield was obtained in a proteose peptone-yeast extract medium. Optimal conditions for growth and beta-lactamase production were obtained at 37 C and pH 7.0. The beta-lactamase was released into the surrounding medium during the growth period to about 50%. Osmotic shock released about 20% of the total activity, and remaining activity was found in the cytoplasmic fraction. Substrate profile studies on four beta-lactamase-producing strains showed that the enzymes were mainly cephalosporinases. They are inhibited by cloxacillin, p-chloromercuribenzoate, and iodine. Analytical isoelectric focusing in polyacrylamide gel gave an isoelectric point of 4.9 +/- 0.2 for three of the strains and 5.6 +/- 0.2 for one. Comparison with beta-lactamases from aerobic gram-negative species with regard to isoelectric points showed no similarities. Also the molecular weight of the beta-lactamase from strain B70 of 43,000 indicates that this is a new class of beta-lactamase.

  18. Self-organization in space plasma: formation of magnetic shear in current sheets

    NASA Astrophysics Data System (ADS)

    Zelenyi, Lev; Delcourt, Dominique; Mingalev, Oleg; Malova, Helmi; Popov, Victor; Grigorenko, Elena; Petrukovich, Anatoli

    2016-07-01

    Thin current sheets are plasma structures that usually appear near reconnection regions. The presence of the shear magnetic field is characteristic for these structures. Self-consistent kinetic model of magnetotail thin current sheet (TCS) is used to understand the mechanisms of self-organization of sheared thin current sheets in a space plasma. It is shown that these configurations appear as a result of self-consistent evolution of some initial magnetic perturbation at current sheet center. Two general shapes of shear TCS components are found as a function of the transverse coordinate: symmetric and antisymmetric. We show that TCS formation goes together with the emergence of field-aligned currents in the center of the current sheet, as a result of north-south asymmetry of quasi-adiabatic ion motions. Ion drift currents can also contribute to the magnetic shear evolution, but their role is much less significant, their contribution depending upon the normal component Bz and the amplitude of the initial perturbation in TCS. Parametric maps illustrating different types of TCS equilibria are presented.

  19. Research of vacancy defect formation on the surface of two-dimensional boron sheets

    NASA Astrophysics Data System (ADS)

    Boroznina, E. V.; Zhiganova, T. A.; Boroznin, S. V.

    2015-01-01

    Mechanism of vacancy defect formation on the surface of two types of BS: triangular BS (TBS), α-sheet (αBS) have been calculated within the model of molecular cluster with the use of quantum chemical MNDO scheme. The process of atomic vacancy formation of BS has been modeled by step-by-step abstraction of one central boron atom. Incremental method allowed us to build energy curves for vacancy formation process. The process of vacancy migration on the BS surface has also have been investigated, and more probable paths of migration have been found.

  20. Formation and Reconnection of Three-Dimensional Current Sheets in the Solar Corona

    NASA Technical Reports Server (NTRS)

    Edmondson, J. K.; Antiochos, S. K.; DeVore, C. R.; Zurbuchen, T. H.

    2010-01-01

    Current-sheet formation and magnetic reconnection are believed to be the basic physical processes responsible for much of the activity observed in astrophysical plasmas, such as the Sun s corona. We investigate these processes for a magnetic configuration consisting of a uniform background field and an embedded line dipole, a topology that is expected to be ubiquitous in the corona. This magnetic system is driven by a uniform horizontal flow applied at the line-tied photosphere. Although both the initial field and the driver are translationally symmetric, the resulting evolution is calculated using a fully three-dimensional magnetohydrodynamic (3D MHD) simulation with adaptive mesh refinement that resolves the current sheet and reconnection dynamics in detail. The advantage of our approach is that it allows us to apply directly the vast body of knowledge gained from the many studies of 2D reconnection to the fully 3D case. We find that a current sheet forms in close analogy to the classic Syrovatskii 2D mechanism, but the resulting evolution is different than expected. The current sheet is globally stable, showing no evidence for a disruption or a secondary instability even for aspect ratios as high as 80:1. The global evolution generally follows the standard Sweet- Parker 2D reconnection model except for an accelerated reconnection rate at a very thin current sheet, due to the tearing instability and the formation of magnetic islands. An interesting conclusion is that despite the formation of fully 3D structures at small scales, the system remains close to 2D at global scales. We discuss the implications of our results for observations of the solar corona. Subject Headings: Sun: corona Sun: magnetic fields Sun: reconnection

  1. Multinuclear NMR studies of the flavodoxin from Anabaena 7120:. beta. -sheet structure and the flavin mononucleotide binding site

    SciTech Connect

    Stockman, B.J.

    1989-01-01

    A concerted approach to primary {sup 1}H, {sup 13}C, and {sup 15}N nuclear magnetic resonance assignments in proteins was developed. The method requires enrichment of the protein with {sup 13}C and {sup 15}N. The technique relies on the comparison of data sets from NMR experiments that correlate various nuclei: {sup 13}C({sup 13}C) double quantum correlations, {sup 1}H({sup 13}C) and {sup 1}H({sup 15}N) single bond correlations, and {sup 1}H({sup 13}C) and {sup 1}H({sup 15}N) multiple bond correlations. Comparison of data sets increases the number of resonances that can be assigned and improves assignment confidence. By combined use of these and conventional NMR techniques, sequential assignments were made for the {beta}-sheet and flavin mononucleotide (FMN) binding site residues in flavodoxin from Anabaena 7120. The {beta}-sheet structure was found to be similar to that seen in the crystal structure of Anacystis nidulans flavodoxin. In the FMN binding site, a total of 69 NOEs were identified: eight between protons of FMN, 36 between protons of binding site residues, and 25 between protons of FMN and protein. These constraints were used to determine the localized solution structure of the flavin binding site. The electronic environment and conformation of the protein-bound isoalloxazine ring were investigated by determining chemical shifts and coupling constants for the ring atoms. The carbonyl edge of the flavin ring was found to be slightly polarized by hydrogen bonding to the protein. The xylene ring was found to be nonplanar. The C{sup 6}-N{sup 5} region of the flavin appears to be solvent accessible.

  2. Probing the Nanosecond Dynamics of a Designed Three-Stranded Beta-Sheet with a Massively Parallel Molecular Dynamics Simulation

    PubMed Central

    Voelz, Vincent A.; Luttmann, Edgar; Bowman, Gregory R.; Pande, Vijay S.

    2009-01-01

    Recently a temperature-jump FTIR study of a designed three-stranded sheet showing a fast relaxation time of ~140 ± 20 ns was published. We performed massively parallel molecular dynamics simulations in explicit solvent to probe the structural events involved in this relaxation. While our simulations produce similar relaxation rates, the structural ensemble is broad. We observe the formation of turn structure, but only very weak interaction in the strand regions, which is consistent with the lack of strong backbone-backbone NOEs in previous structural NMR studies. These results suggest that either DPDP-II folds at time scales longer than 240 ns, or that DPDP-II is not a well-defined three-stranded β-sheet. This work also provides an opportunity to compare the performance of several popular forcefield models against one another. PMID:19399235

  3. World Sheet Commuting beta-gamma CFT and Non-Relativistic StringTheories

    SciTech Connect

    Kim, Bom Soo

    2007-08-30

    We construct a sigma model in two dimensions with Galilean symmetry in flat target space similar to the sigma model of the critical string theory with Lorentz symmetry in 10 flat spacetime dimensions. This is motivated by the works of Gomis and Ooguri[1] and Danielsson et. al.[2, 3]. Our theory is much simpler than their theory and does not assume a compact coordinate. This non-relativistic string theory has a bosonic matter {beta}{gamma} CFT with the conformal weight of {beta} as 1. It is natural to identify time as a linear combination of {gamma} and {bar {gamma}} through an explicit realization of the Galilean boost symmetry. The angle between {gamma} and {bar {gamma}} parametrizes one parameter family of selection sectors. These selection sectors are responsible for having a non-relativistic dispersion relation without a nontrivial topology in the non-relativistic setup, which is one of the major differences from the previous works[1, 2, 3]. This simple theory is the non-relativistic analogue of the critical string theory, and there are many different avenues ahead to be investigated. We mention a possible consistent generalization of this theory with different conformal weights for the {beta}{gamma} CFT. We also mention supersymmetric generalizations of these theories.

  4. The crystal structures of [Met5]enkephalin and a third form of [Leu5]enkephalin: observations of a novel pleated beta-sheet.

    PubMed Central

    Griffin, J F; Langs, D A; Smith, G D; Blundell, T L; Tickle, I J; Bedarkar, S

    1986-01-01

    The structures of [Met5]enkephalin (Tyr-Gly-Gly-Phe-Met) and [Leu5]enkephalin (Tyr-Gly-Gly-Phe-Leu) have been determined from single crystal x-ray diffraction data and refined to residuals of 0.100 and 0.092, respectively. The [Met5]enkephalin structure consists of dimers forming antiparallel beta-sheets extending in the monoclinic ac plane with 10.6 water molecules per dimer. The two molecules, related by pseudo two-fold axes, have similar backbone conformations and similar tyrosine and phenylalanine side-chain conformations. Both methionine residues are disordered and the disorder is different in the two independent molecules. Additional hydrogen bonds connect adjacent dimers to form infinite sheets normal to the b axis. The water molecules are found mainly in the interstices between the sheets. [Leu5]Enkephalin crystallizes as a monohydrate that is isomorphous with the [Met5]enkephalin structure with respect to the beta-sheet but different with respect to the tyrosine and phenylalanine side-chain conformations and water content. The peptide chains in both structures are fully extended and more nearly planar than pleated. The planes of the peptide chains in the dimers form an angle of 143.3 degrees with one another in [Met5]enkephalin and 156.0 degrees in [Leu5]enkephalin. This produces a zigzag pattern or pleat in the beta-sheets perpendicular to the direction of the peptide chains and, therefore, perpendicular to the normal beta-sheet pleat. The average repeat distance between Ni and Ni+2 in the peptide chains of both structures is 7.10 A, versus an ideal value of 6.68 A. PMID:3458181

  5. Mechanism of IAPP amyloid fibril formation involves an intermediate with a transient β-sheet.

    PubMed

    Buchanan, Lauren E; Dunkelberger, Emily B; Tran, Huong Q; Cheng, Pin-Nan; Chiu, Chi-Cheng; Cao, Ping; Raleigh, Daniel P; de Pablo, Juan J; Nowick, James S; Zanni, Martin T

    2013-11-26

    Amyloid formation is implicated in more than 20 human diseases, yet the mechanism by which fibrils form is not well understood. We use 2D infrared spectroscopy and isotope labeling to monitor the kinetics of fibril formation by human islet amyloid polypeptide (hIAPP or amylin) that is associated with type 2 diabetes. We find that an oligomeric intermediate forms during the lag phase with parallel β-sheet structure in a region that is ultimately a partially disordered loop in the fibril. We confirm the presence of this intermediate, using a set of homologous macrocyclic peptides designed to recognize β-sheets. Mutations and molecular dynamics simulations indicate that the intermediate is on pathway. Disrupting the oligomeric β-sheet to form the partially disordered loop of the fibrils creates a free energy barrier that is the origin of the lag phase during aggregation. These results help rationalize a wide range of previous fragment and mutation studies including mutations in other species that prevent the formation of amyloid plaques.

  6. Simulation of the β- to α-sheet transition results in a twisted sheet for antiparallel and an α-nanotube for parallel strands: implications for amyloid formation.

    PubMed

    Hayward, Steven; Milner-White, E James

    2011-11-01

    α-sheet has been proposed to be the main constituent of the toxic amyloid intermediate. Molecular dynamics simulations on proteins known to be involved in amyloid diseases have demonstrated that β-sheet can, under certain conditions, spontaneously convert to α-sheet via ββ→α(R)α(L) peptide-plane flipping. Using torsion-angle driving to simulate this flip the transition has been investigated for parallel and antiparallel sheets. Concerted and sequential flipping processes were simulated, the former allowing direct calculation of helical parameters. For antiparallel sheet, the strands tend to splay apart during the transition. This can be understood by consideration of the geometry of repeating dipeptide conformations. At the end of the transition antiparallel α-sheet is slightly twisted, comprising gently curving strands. In parallel sheet, the strands maintain identical conformations and stay hydrogen bonded during the transition as they curl up to suggest a hitherto unseen structure, the multi-helix α-nanotube. Intriguingly, the α-nanotube has some of the characteristics of the parallel β-helix, a single-helix structure also implicated in amyloid. Unlike the β-helix, α-nanotube formation could involve identical strands aligning with each other in register as in most amyloids.

  7. Efficient traversal of beta-sheet protein folding pathways using ensemble models.

    PubMed

    Shenker, Solomon; O'Donnell, Charles W; Devadas, Srinivas; Berger, Bonnie; Waldispühl, Jérôme

    2011-11-01

    Molecular dynamics (MD) simulations can now predict ms-timescale folding processes of small proteins; however, this presently requires hundreds of thousands of CPU hours and is primarily applicable to short peptides with few long-range interactions. Larger and slower-folding proteins, such as many with extended β-sheet structure, would require orders of magnitude more time and computing resources. Furthermore, when the objective is to determine only which folding events are necessary and limiting, atomistic detail MD simulations can prove unnecessary. Here, we introduce the program tFolder as an efficient method for modelling the folding process of large β-sheet proteins using sequence data alone. To do so, we extend existing ensemble β-sheet prediction techniques, which permitted only a fixed anti-parallel β-barrel shape, with a method that predicts arbitrary β-strand/β-strand orientations and strand-order permutations. By accounting for all partial and final structural states, we can then model the transition from random coil to native state as a Markov process, using a master equation to simulate population dynamics of folding over time. Thus, all putative folding pathways can be energetically scored, including which transitions present the greatest barriers. Since correct folding pathway prediction is likely determined by the accuracy of contact prediction, we demonstrate the accuracy of tFolder to be comparable with state-of-the-art methods designed specifically for the contact prediction problem alone. We validate our method for dynamics prediction by applying it to the folding pathway of the well-studied Protein G. With relatively very little computation time, tFolder is able to reveal critical features of the folding pathways which were only previously observed through time-consuming MD simulations and experimental studies. Such a result greatly expands the number of proteins whose folding pathways can be studied, while the algorithmic integration of

  8. Venus - Volcanism and rift formation in Beta Regio

    NASA Astrophysics Data System (ADS)

    Campbell, D. B.; Head, J. W.; Harmon, J. K.; Hine, A. A.

    1984-10-01

    A new high-resolution radar image of Beta Regio, a Venus highland area, confirms the presence of a major tectonic rift system and associated volcanic activity. The lack of identifiable impact craters, together with the apparent superposition of the Theia Mons volcanic structure on the rift system, suggest that at least some of the volcanic activity occurred in relatively recent geologic time. The presence of topographically similar highland areas elsewhere on Venus (Aphrodite Terra, Dali Chasma, and Diana Chasma) suggests that rifting and volcanism are significant processes on Venus.

  9. Landscape formation by past continental ice sheets: insights into the subglacial environment

    NASA Astrophysics Data System (ADS)

    Piotrowski, Jan A.

    2014-05-01

    Glaciers and ice sheets are known as most powerful, climatically driven agents of large-scale sediment redistribution and landscape formation in the Earth system. During the Quaternary, repeated waxing and waning of continental ice sheets contributed to profound reshaping of the Earth surface and set the scene for the development of ecosystems in the post-glacial time. Despite the well-established impact of glaciers on the upper lithosphere the specific processes of glacial erosion, transport and deposition and the formation landforms at the ice-bed interface are contentious. In particular, the relative importance of direct ice impact versus the impact of glacial meltwater is highly controversial. Here, we focus on the southern peripheral area of the Scandinavian Ice Sheet hosting thick successions of soft, deformable sediments and examine some spectacular sediment/landform assemblages found nowadays in both terrestrial and marine settings to illustrate the nature of the subglacial processes. In order to decipher the past ice sheet behavior field, experimental and numerical approaches are combined. It is shown that the strength of the coupling between the ice and the bed that controls the response of the substratum to ice overriding and stress propagation depends primarily on the ability of the glacial system to evacuate meltwater from ice-bed interface. Strong coupling, locally enhanced by subglacial permafrost resulted in deeply rooted (100's of meters) glaciotectonic deformation reflected on the surface as ice-shoved hills whereas weak coupling promoted by water accumulating under the ice triggered the formation of deep (100's of meters) tunnel valley networks. Under the arteries of fast-flowing ice known as palaeo-ice streams, remoulding of soft sediments generated mega-scale glacial lineations and drumlins that hold the key to understanding glacier dynamics. The subglacial environment is envisaged as a four-dimensional mosaic of stable and deforming spots

  10. Current sheet Formation in a Conical Theta Pinch Faraday Accelerator with Radio-Frequency Assisted Discharge

    NASA Technical Reports Server (NTRS)

    Hallock, Ashley K.; Choueiri, Edgar Y.; Polzin, Kurt A.

    2007-01-01

    The inductive formation of current sheets in a conical theta pinch FARAD (Faraday Accelerator with Radio-frequency Assisted Discharge) thruster is investigated experimentally with time-integrated photography. The goal is to help in understanding the mechanisms and conditions controlling the strength and extent of the current sheet, which are two indices important for FARAD as a propulsion concept. The profiles of these two indices along the inside walls of the conical acceleration coil are assumed to be related to the profiles of the strength and extent of the luminosity pattern derived from photographs of the discharge. The variations of these profiles as a function of uniform back-fill neutral pressure (with no background magnetic field and all parameters held constant) provided the first clues on the nature and qualitative dependencies of current sheet formation. It was found that there is an optimal pressure for which both indices reach a maximum and that the rate of change in these indices with pressure differs on either side of this optimal pressure. This allowed the inference that current sheet formation follows a Townsend-like breakdown mechanism modified by the existence of a finite pressure-dependent radio-frequency-generated electron density background. The observation that the effective location of the luminosity pattern favors the exit-half of the conical coil is explained as the result of the tendency of the inductive discharge circuit to operate near its minimal self-inductance. Movement of the peak in the luminosity pattern towards the upstream side of the cone with increasing pressure is believed to result from the need of the circuit to compensate for the increase in background plasma resistivity due to increasing pressure.

  11. Formation and Degradation of Beta-casomorphins in Dairy Processing.

    PubMed

    Nguyen, Duc Doan; Johnson, Stuart Keith; Busetti, Francesco; Solah, Vicky Ann

    2015-01-01

    Milk proteins including casein are sources of peptides with bioactivity. One of these peptides is beta-casomorphin (BCM) which belongs to a group of opioid peptides formed from β-casein variants. Beta-casomorphin 7 (BCM7) has been demonstrated to be enzymatically released from the A1 or B β-casein variant. Epidemiological evidence suggests the peptide BCM 7 is a risk factor for development of human diseases, including increased risk of type 1 diabetes and cardiovascular diseases but this has not been thoroughly substantiated by research studies. High performance liquid chromatography coupled to UV-Vis and mass spectrometry detection as well as enzyme-linked immunosorbent assay (ELISA) has been used to analyze BCMs in dairy products. BCMs have been detected in raw cow's milk and human milk and a variety of commercial cheeses, but their presence has yet to be confirmed in commercial yoghurts. The finding that BCMs are present in cheese suggests they could also form in yoghurt, but be degraded during yoghurt processing. Whether BCMs do form in yoghurt and the amount of BCM forming or degrading at different processing steps needs further investigation and possibly will depend on the heat treatment and fermentation process used, but it remains an intriguing unknown.

  12. Formation and Degradation of Beta-casomorphins in Dairy Processing

    PubMed Central

    Nguyen, Duc Doan; Johnson, Stuart Keith; Busetti, Francesco; Solah, Vicky Ann

    2015-01-01

    Milk proteins including casein are sources of peptides with bioactivity. One of these peptides is beta-casomorphin (BCM) which belongs to a group of opioid peptides formed from β-casein variants. Beta-casomorphin 7 (BCM7) has been demonstrated to be enzymatically released from the A1 or B β-casein variant. Epidemiological evidence suggests the peptide BCM 7 is a risk factor for development of human diseases, including increased risk of type 1 diabetes and cardiovascular diseases but this has not been thoroughly substantiated by research studies. High performance liquid chromatography coupled to UV-Vis and mass spectrometry detection as well as enzyme–linked immunosorbent assay (ELISA) has been used to analyze BCMs in dairy products. BCMs have been detected in raw cow's milk and human milk and a variety of commercial cheeses, but their presence has yet to be confirmed in commercial yoghurts. The finding that BCMs are present in cheese suggests they could also form in yoghurt, but be degraded during yoghurt processing. Whether BCMs do form in yoghurt and the amount of BCM forming or degrading at different processing steps needs further investigation and possibly will depend on the heat treatment and fermentation process used, but it remains an intriguing unknown. PMID:25077377

  13. Formation and Degradation of Beta-casomorphins in Dairy Processing.

    PubMed

    Nguyen, Duc Doan; Johnson, Stuart Keith; Busetti, Francesco; Solah, Vicky Ann

    2015-01-01

    Milk proteins including casein are sources of peptides with bioactivity. One of these peptides is beta-casomorphin (BCM) which belongs to a group of opioid peptides formed from β-casein variants. Beta-casomorphin 7 (BCM7) has been demonstrated to be enzymatically released from the A1 or B β-casein variant. Epidemiological evidence suggests the peptide BCM 7 is a risk factor for development of human diseases, including increased risk of type 1 diabetes and cardiovascular diseases but this has not been thoroughly substantiated by research studies. High performance liquid chromatography coupled to UV-Vis and mass spectrometry detection as well as enzyme-linked immunosorbent assay (ELISA) has been used to analyze BCMs in dairy products. BCMs have been detected in raw cow's milk and human milk and a variety of commercial cheeses, but their presence has yet to be confirmed in commercial yoghurts. The finding that BCMs are present in cheese suggests they could also form in yoghurt, but be degraded during yoghurt processing. Whether BCMs do form in yoghurt and the amount of BCM forming or degrading at different processing steps needs further investigation and possibly will depend on the heat treatment and fermentation process used, but it remains an intriguing unknown. PMID:25077377

  14. In Search of the Attributes Responsible for Sliver Formation in Cold Rolled Steel Sheets

    NASA Astrophysics Data System (ADS)

    Mohanty, Itishree; Das, Prasun; Bhattacharjee, Debashish; Datta, Shubhabrata

    2016-06-01

    Surface quality is one of the most important characteristics of cold rolled (CR) steel sheets for its application in consumer goods industries. The actual cause of sliver formation is very difficult to determine, as it is revealed only after the final cold rolling of the steel. A thorough investigation on searching the root cause of sliver formation in CR steel is done here using several statistical tools towards mining the industrial data for extraction of knowledge. As the complex interactions between the variables make it difficult to identify the cause, it is seen that findings from different techniques differed to a certain extent. Still it is revealed that 21 variables could be short listed as major contributor for sliver formation, but those are found to be from all the areas of the processing. This leads to the conclusion that no particular process variable or particular processing could be held responsible for sliver formation.

  15. Addition of Adipose-Derived Stem Cells to Mesenchymal Stem Cell Sheets Improves Bone Formation at an Ectopic Site

    PubMed Central

    Wang, Zhifa; Li, Zhijin; Dai, Taiqiang; Zong, Chunlin; Liu, Yanpu; Liu, Bin

    2016-01-01

    To determine the effect of adipose-derived stem cells (ADSCs) added to bone marrow-derived mesenchymal stem cell (MSC) sheets on bone formation at an ectopic site. We isolated MSCs and ADSCs from the same rabbits. We then prepared MSC sheets for implantation with or without ADSCs subcutaneously in the backs of severe combined immunodeficiency (SCID) mice. We assessed bone formation at eight weeks after implantation by micro-computed tomography and histological analysis. In osteogenic medium, MSCs grew to form multilayer sheets containing many calcium nodules. MSC sheets without ADSCs formed bone-like tissue; although neo-bone and cartilage-like tissues were sparse and unevenly distributed by eight weeks after implantation. In comparison, MSC sheets with ADSCs promoted better bone regeneration as evidenced by the greater density of bone, increased mineral deposition, obvious formation of blood vessels, large number of interconnected ossified trabeculae and woven bone structures, and greater bone volume/total volume within the composite constructs. Our results indicate that although sheets of only MSCs have the potential to form tissue engineered bone at an ectopic site, the addition of ADSCs can significantly increase the osteogenic potential of MSC sheets. Thus, the combination of MSC sheets with ADSCs may be regarded as a promising therapeutic strategy to stimulate bone regeneration. PMID:26848656

  16. Addition of Adipose-Derived Stem Cells to Mesenchymal Stem Cell Sheets Improves Bone Formation at an Ectopic Site.

    PubMed

    Wang, Zhifa; Li, Zhijin; Dai, Taiqiang; Zong, Chunlin; Liu, Yanpu; Liu, Bin

    2016-01-01

    To determine the effect of adipose-derived stem cells (ADSCs) added to bone marrow-derived mesenchymal stem cell (MSC) sheets on bone formation at an ectopic site. We isolated MSCs and ADSCs from the same rabbits. We then prepared MSC sheets for implantation with or without ADSCs subcutaneously in the backs of severe combined immunodeficiency (SCID) mice. We assessed bone formation at eight weeks after implantation by micro-computed tomography and histological analysis. In osteogenic medium, MSCs grew to form multilayer sheets containing many calcium nodules. MSC sheets without ADSCs formed bone-like tissue; although neo-bone and cartilage-like tissues were sparse and unevenly distributed by eight weeks after implantation. In comparison, MSC sheets with ADSCs promoted better bone regeneration as evidenced by the greater density of bone, increased mineral deposition, obvious formation of blood vessels, large number of interconnected ossified trabeculae and woven bone structures, and greater bone volume/total volume within the composite constructs. Our results indicate that although sheets of only MSCs have the potential to form tissue engineered bone at an ectopic site, the addition of ADSCs can significantly increase the osteogenic potential of MSC sheets. Thus, the combination of MSC sheets with ADSCs may be regarded as a promising therapeutic strategy to stimulate bone regeneration.

  17. Inhibition of fibril formation in beta-amyloid peptide by a novel series of benzofurans.

    PubMed Central

    Howlett, D R; Perry, A E; Godfrey, F; Swatton, J E; Jennings, K H; Spitzfaden, C; Wadsworth, H; Wood, S J; Markwell, R E

    1999-01-01

    A series of benzofuran derivatives have been identified as inhibitors of fibril formation in the beta-amyloid peptide. The activity of these compounds has been assessed by a novel fibril-formation-specific immunoassay and for their effects on the production of a biologically active fibril product. The inhibition afforded by the compounds seems to be associated with their binding to beta-amyloid, as identified by scintillation proximity binding assay. Binding assays and NMR studies also indicate that the inhibition is associated with self-aggregation of the compounds. There is a close correlation between the activity of the benzofurans as inhibitors of fibril formation and their ability to bind to beta-amyloid. Non-benzofuran inhibitors of the fibril formation process do not seem to bind to the same site on the beta-amyloid molecule as the benzofurans. Thus a specific recognition site might exist for benzofurans on beta-amyloid, binding to which seems to interfere with the ability of the peptide to form fibrils. PMID:10229684

  18. Interactive property of large thrust sheets with footwall rocks—the Sub thrust interactive duplex hypothesis: A mechanism of dome formation in thrust sheets

    NASA Astrophysics Data System (ADS)

    Hatcher, Robert D.

    1991-06-01

    Recently acquired Appalachian Ultradeep Core Hole (ADCOH) Project site investigation seismic reflection data and geologic data from the Appalachians and several other orogenic belts suggest an important mutually interdependent relationship exists between emplacement of large crystalline thrust sheets and the deforming foreland rocks beneath. This relationship suggests isolated domes beneath crystalline thrust sheets may be produced by passive folding of the sheet as a result of formation of an antiformal stack duplex in the platform sedimentary sequence beneath. Suggestions that domes in crystalline thrust sheets formed by interference of late open folds is doubtlessly still valid in places, but the platform duplex mechanism is probably also valid to explain the late doming of many crystalline and other large thrust sheets. The dome beneath the Shooting Creek and Brasstown Bald windows in the ADCOH site region is imaged as an antiformal stack duplex at depth. The Tallulah Falls dome, Grandfather Mountain and Mountain City windows, and Smokies Foothills duplex in the site region and elsewhere in the southern Blue Ridge are all late isolated domes and all are probably or demonstrably underlain by antiformal stack duplexes beneath the Blue Ridge-Piedmont composite crystalline thrust sheet. The Assynt window and footwall duplex benath the Arnabol and Moine thrusts in Scotland, and the Engadine window in the Alps may be similar structures.

  19. Concentration-dependent inhibitory effects of apolipoprotein E on Alzheimer's beta-amyloid fibril formation in vitro.

    PubMed

    Naiki, H; Gejyo, F; Nakakuki, K

    1997-05-20

    Recently, many research groups have examined the effect of apolipoprotein E (apoE) on beta-amyloid fibril (betaAf) formation in vitro. However, their data were somewhat controversial and no exact kinetic assessment of the role of apoE has thus far been available. We examined the effect of human apoE on betaAf formation in vitro, starting with various concentrations of freshly prepared beta-amyloid(1-40) (beta1-40) and using fluorescence spectroscopy with thioflavine T. When 50 microM of beta1-40 was incubated with a 1:1000 to 1:100 molar ratio of apoE, a dose-dependent inhibitory effect of apoE was observed. Both the nucleation and extension phases of betaAf formation in vitro were inhibited by apoE. On the other hand, when 300 microM of beta1-40 was incubated with a 1:100 molar ratio of apoE, the inhibitory effect of apoE was completely abolished. We then focused our study on the kinetics of the inhibitory effect of apoE on the extension phase of betaAf formation in vitro, utilizing the recently established first-order kinetic model of betaAf extension in vitro [Naiki, H., & Nakakuki, K. (1996) Lab. Invest. 74, 374-383]. The mathematical treatment of the data suggests that apoE inhibits the extension of betaAf in vitro, by making a complex with beta1-40, thus eliminating free beta1-40 from the reaction mixture. The equilibrium association constant with beta1-40 was practically the same among the three major recombinant apoE isoforms. These results indicate that the effects of apoE on betaAf formation in vitro is differential and could settle some of the controversy about beta-amyloid-apoE interaction in vitro.

  20. Beta-Sheet-Forming, Self-Assembled Peptide Nanomaterials towards Optical, Energy, and Healthcare Applications.

    PubMed

    Kim, Sungjin; Kim, Jae Hong; Lee, Joon Seok; Park, Chan Beum

    2015-08-12

    Peptide self-assembly is an attractive route for the synthesis of intricate organic nanostructures that possess remarkable structural variety and biocompatibility. Recent studies on peptide-based, self-assembled materials have expanded beyond the construction of high-order architectures; they are now reporting new functional materials that have application in the emerging fields such as artificial photosynthesis and rechargeable batteries. Nevertheless, there have been few reviews particularly concentrating on such versatile, emerging applications. Herein, recent advances in the synthesis of self-assembled peptide nanomaterials (e.g., cross β-sheet-based amyloid nanostructures, peptide amphiphiles) are selectively reviewed and their new applications in diverse, interdisciplinary fields are described, ranging from optics and energy storage/conversion to healthcare. The applications of peptide-based self-assembled materials in unconventional fields are also highlighted, such as photoluminescent peptide nanostructures, artificial photosynthetic peptide nanomaterials, and lithium-ion battery components. The relation of such functional materials to the rapidly progressing biomedical applications of peptide self-assembly, which include biosensors/chips and regenerative medicine, are discussed. The combination of strategies shown in these applications would further promote the discovery of novel, functional, small materials. PMID:25929870

  1. Choline kinase beta is required for normal endochondral bone formation

    PubMed Central

    Li, Zhuo; Wu, Gengshu; Sher, Roger B.; Khavandgar, Zohreh; Hermansson, Martin; Cox, Gregory A.; Doschak, Michael R.; Murshed, Monzur; Beier, Frank; Vance, Dennis E.

    2014-01-01

    Background Choline kinase has three isoforms encoded by the genes Chka and Chkb. Inactivation of Chka in mice results in embryonic lethality, whereas Chkb−/− mice display neonatal forelimb bone deformations. Methods To understand the mechanisms underlying the bone deformations, we compared the biology and biochemistry of bone formation from embryonic to young adult wild-type (WT) and Chkb−/− mice. Results The deformations are specific to the radius and ulna during the late embryonic stage. The radius and ulna of Chkb−/− mice display expanded hypertrophic zones, unorganized proliferative columns in their growth plates, and delayed formation of primary ossification centers. The differentiation of chondrocytes of Chkb−/− mice was impaired, as was chondrocyte proliferation and expression of matrix metalloproteinases 9 and 13. In chondrocytes from Chkb−/− mice, phosphatidylcholine was slightly lower than in WT mice whereas the amount of phosphocholine was decreased by approximately 75%. In addition, the radius and ulna from Chkb−/− mice contained fewer osteoclasts along the cartilage/bone interface. Conclusions Chkb has a critical role in the normal embryogenic formation of the radius and ulna in mice. PMID:24637075

  2. Low cost fabrication of sheet structure using a new beta titanium alloy, Ti-15V-3Cr-3Al-3Sn

    NASA Technical Reports Server (NTRS)

    Kaneko, R. S.; Davis, G. W.; Woods, C. A.; Royster, D. M.

    1982-01-01

    Development efforts have been undertaken to improve the processing and structural efficiencies of advanced cold-formable beta Ti alloys, using the standard, hot-formed and rivetted construction of Ti-6Al-4V sheet structures as a basis for comparison. Ti-15V-3Cr-3Al-3Sn (Ti-15-3) beta alloy is formable, brazable and weldable in the solution-treated condition, and after aging displays mechanical properties suitable for postulated service in the -65 to 600 F temperature range. A novel methodology using cold-formed Ti-15-3 stringers and Ti-6Al-4V face sheets that are joined by means of an out-of-furnace isothermal brazing process, followed by low temperature aging, can reduce production costs by as much as 28 per cent. Structural efficiency has been demonstrated in room and elevated temperature crippling tests of small skin-stringer assemblies.

  3. A revised set of potentials for beta-turn formation in proteins.

    PubMed Central

    Hutchinson, E. G.; Thornton, J. M.

    1994-01-01

    Three thousand eight hundred ninety-nine beta-turns have been identified and classified using a nonhomologous data set of 205 protein chains. These were used to derive beta-turn positional potentials for turn types I' and II' for the first time and to provide updated potentials for formation of the more common types I, II, and VIII. Many of the sequence preferences for each of the 4 positions in turns can be rationalized in terms of the formation of stabilizing hydrogen bonds, preferences for amino acids to adopt a particular conformation in phi, psi space, and the involvement of turn types I' and II' in beta-hairpins. Only 1,632 (42%) of the turns occur in isolation; the remainder have at least 1 residue in common with another turn and have hence been classified as multiple turns. Several types of multiple turn have been identified and analyzed. PMID:7756980

  4. Calcofluor fluorescence assay for wort beta-glucan in a microplate format

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The widely-used fluorescent (Calcofluor) flow injection analysis method for determining the concentrations of beta-glucans in Congress worts from barley malts is adapted to microplate format. Adaptation of the Calcofluor assay to use widely available fluorescent microplate readers makes the assay m...

  5. Aluminium and iron, but neither copper nor zinc, are key to the precipitation of beta-sheets of Abeta_{42} in senile plaque cores in Alzheimer's disease.

    PubMed

    Exley, Christopher

    2006-11-01

    A number of metals including Fe(II)/Fe(III), Al(III), Zn(II) and Cu(II) are found co-localised with beta-sheets of Abeta_{42} in senile plaque cores in AD brain. We know neither why nor how the co-localisation takes place or, indeed, if it is entirely aberrant or partly protective. There are data from in vitro studies which may begin to explain some of these unanswered questions and in considering these I have summised that Al(III) and Fe(III)/Fe(II) are directly involved in the precipitation of beta-sheets of Abeta_{42} in senile plaque cores whereas the presence of Cu(II) and Zn(II) is adventitious. The co-deposition of Al(III), Fe(III) and beta-sheets of Abeta_{42} could act as a source of reactive oxygen species and begin to explain some of the oxidative damage found in the immediate vicinity of senile plaques. Whether such metal-Abeta_{42} synergisms are an integral part of the aetiology of AD remains to be confirmed.

  6. Effect of secondary structure on the potential of mean force for poly-L-lysine in the alpha-Helix and beta-sheet conformations

    SciTech Connect

    Grigsby, J.J.; Blanch, H.W.; Prausnitz, J.M.

    2001-10-30

    Because poly-L-lysine (PLL) can exist in the {alpha}-helix or {beta}-sheet conformation depending on solution preparation and solution conditions, PLL is a suitable candidate to probe the dependence of protein interactions on secondary structure. The osmotic second virial coefficient and weight-average molecular weight are reported from low-angle laser-light scattering measurements for PLL as a function of NaCl concentration, pH, and {alpha}-helix or {beta}-sheet content. Interactions between PLL molecules become more attractive as salt concentration increases due to screening of PLL charge by salt ions and at low salt concentration become more attractive as pH increases due to decreased net charge on PLL. The experimental results show that interactions are stronger for the {beta}-sheet conformation than for the {alpha}-helix conformation. A spherically-symmetric model for the potential of mean force is used to account for specific interactions not described by DLVO theory and to show how differences in secondary structure affect PLL interactions.

  7. High-Resolution Structure of a Self-Assembly-Competent Form of a Hydrophobic Peptide Captured in a Soluble [beta]-Sheet Scaffold

    SciTech Connect

    Makabe, Koki; Biancalana, Matthew; Yan, Shude; Tereshko, Valentina; Gawlak, Grzegorz; Miller-Auer, Hélène; Meredith, Stephen C.; Koide, Shohei

    2010-02-08

    {beta}-Rich self-assembly is a major structural class of polypeptides, but still little is known about its atomic structures and biophysical properties. Major impediments for structural and biophysical studies of peptide self-assemblies include their insolubility and heterogeneous composition. We have developed a model system, termed peptide self-assembly mimic (PSAM), based on the single-layer {beta}-sheet of Borrelia outer surface protein A. PSAM allows for the capture of a defined number of self-assembly-like peptide repeats within a water-soluble protein, making structural and energetic studies possible. In this work, we extend our PSAM approach to a highly hydrophobic peptide sequence. We show that a penta-Ile peptide (Ile{sub 5}), which is insoluble and forms {beta}-rich self-assemblies in aqueous solution, can be captured within the PSAM scaffold in a form capable of self-assembly. The 1.1-{angstrom} crystal structure revealed that the Ile{sub 5} stretch forms a highly regular {beta}-strand within this flat {beta}-sheet. Self-assembly models built with multiple copies of the crystal structure of the Ile5 peptide segment showed no steric conflict, indicating that this conformation represents an assembly-competent form. The PSAM retained high conformational stability, suggesting that the flat {beta}-strand of the Ile{sub 5} stretch primed for self-assembly is a low-energy conformation of the Ile{sub 5} stretch and rationalizing its high propensity for self-assembly. The ability of the PSAM to 'solubilize' an otherwise insoluble peptide stretch suggests the potential of the PSAM approach to the characterization of self-assembling peptides.

  8. Crystal structure and a twisted beta-sheet conformation of the tripeptide L-leucyl-L-leucyl-L-leucine monohydrate trimethanol solvate: conformation analysis of tripeptides.

    PubMed

    Go, K; Parthasarathy, R

    1995-11-01

    In order to test the helical preference of short oligo-L-leucines, we crystallized the tripeptide L-leucyl-L-leucyl-L-leucine (LLL) and carried out x-ray diffraction studies of it (L-leucyl-L-leucyl-Lleucine)2. 3CH3OH. H2O, (C39H84N6O12), crystallized in the monoclinic system, space group P2(1), cell parameters: a = 12.031(2), b = 15.578(3), c = 14.087(2) A, alpha = 90 degrees, beta = 97.29(1) degrees, gamma = 90 degrees, V = 2618.6 A3, MW = 829.1, Dc = 1.051 g cm-3, R index of 0.057 for 4213 reflections (lambda CuK alpha = 1.5418 A) > 2 sigma. LLL takes up the beta-sheet rather than a helical conformation in the crystalline state. The three methanol molecules and the water molecule that constitute the solvent of crystallization form a network of hydrogen bonds to the LLL molecules and to one another. It is rather remarkable that though A and L have stronger helical preferences than G, neither AAA nor LLL form the crystalline helix but GAL does, indicating that the helical preferences depend on the sequence context. The residue L2 in molecule A and the residues L1 and L3 of molecule B do not show the preferred conformation for forming helices. Further, very remarkably, LLL exhibits a unique supersecondary feature of the protein folding topology, namely the twisted beta-sheet, whereas most short peptides show only the classical beta-sheet conformation.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Mutations that affect coenzyme binding and dimer formation of fungal 17beta-hydroxysteroid dehydrogenase.

    PubMed

    Brunskole, Mojca; Kristan, Katja; Stojan, Jure; Rizner, Tea Lanisnik

    2009-03-25

    The 17beta-hydroxysteroid dehydrogenase from the fungus Cochliobolus lunatus (17beta-HSDcl) is an NADPH-dependent member of the short-chain dehydrogenase/reductase superfamily, and it functions as a dimer that is composed of two identical subunits. By constructing the appropriate mutants, we have examined the M204 residue that is situated in the coenzyme binding pocket, for its role in the binding of the coenzyme NADP(H). We have also studied the importance of hydrophobic interactions through F124, F132, F133 and F177 for 17beta-HSDcl dimer formation. The M204G substitution decreased the catalytic efficiency of 17beta-HSDcl, suggesting that M204 sterically coerces the nicotinamide moiety of the coenzyme into the appropriate position for further hydride transfer. Phenylalanine substitutions introduced at the dimer interface produced inactive aggregates and oligomers with high molecular masses, suggesting that these hydrophobic interactions have important roles in the formation of the active dimer.

  10. Enzyme-catalyzed formation of beta-peptides: beta-peptidyl aminopeptidases BapA and DmpA acting as beta-peptide-synthesizing enzymes.

    PubMed

    Heck, Tobias; Kohler, Hans-Peter E; Limbach, Michael; Flögel, Oliver; Seebach, Dieter; Geueke, Birgit

    2007-09-01

    In recent studies, we discovered that the three beta-peptidyl aminopeptidases, BapA from Sphingosinicella xenopeptidilytica 3-2W4, BapA from S. microcystinivorans Y2, and DmpA from Ochrobactrum anthropi LMG7991, possess the unique feature of cleaving N-terminal beta-amino acid residues from beta- and alpha/beta-peptides. Herein, we investigated the use of the same three enzymes for the reverse reaction catalyzing the oligomerization of beta-amino acids and the synthesis of mixed peptides with N-terminal beta-amino acid residues. As substrates, we employed the beta-homoamino acid derivatives H-beta hGly-pNA, H-beta3 hAla-pNA, H-(R)-beta3 hAla-pNA, H-beta3 hPhe-pNA, H-(R)-beta3 hPhe-pNA, and H-beta3 hLeu-pNA. All three enzymes were capable of coupling the six beta-amino acids to oligomers with chain lengths of up to eight amino acid residues. With the enzyme DmpA as the catalyst, we observed very high conversion rates, which correspond to dimer yields of up to 76%. The beta-dipeptide H-beta3 hAla-beta3 hLeu-OH and the beta/alpha-dipeptide H-beta hGly-His-OH (carnosine) were formed with almost 50% conversion, when a five-fold excess of beta3-homoleucine or histidine was incubated with H-beta3 hAla-pNA and H-beta hGly-pNA, respectively, in the presence of the enzyme BapA from S. microcystinivorans Y2. BapA from S. xenopeptidilytica 3-2W4 turned out to be a versatile catalyst capable of coupling various beta-amino acid residues to the free N-termini of beta- and alpha-amino acids and even to an alpha-tripeptide. Thus, these aminopeptidases might be useful to introduce a beta-amino acid residue as an N-terminal protecting group into a 'natural' alpha-peptide, thereby stabilizing the peptide against degradation by other proteolytic enzymes. PMID:17886858

  11. Enzyme-catalyzed formation of beta-peptides: beta-peptidyl aminopeptidases BapA and DmpA acting as beta-peptide-synthesizing enzymes.

    PubMed

    Heck, Tobias; Kohler, Hans-Peter E; Limbach, Michael; Flögel, Oliver; Seebach, Dieter; Geueke, Birgit

    2007-09-01

    In recent studies, we discovered that the three beta-peptidyl aminopeptidases, BapA from Sphingosinicella xenopeptidilytica 3-2W4, BapA from S. microcystinivorans Y2, and DmpA from Ochrobactrum anthropi LMG7991, possess the unique feature of cleaving N-terminal beta-amino acid residues from beta- and alpha/beta-peptides. Herein, we investigated the use of the same three enzymes for the reverse reaction catalyzing the oligomerization of beta-amino acids and the synthesis of mixed peptides with N-terminal beta-amino acid residues. As substrates, we employed the beta-homoamino acid derivatives H-beta hGly-pNA, H-beta3 hAla-pNA, H-(R)-beta3 hAla-pNA, H-beta3 hPhe-pNA, H-(R)-beta3 hPhe-pNA, and H-beta3 hLeu-pNA. All three enzymes were capable of coupling the six beta-amino acids to oligomers with chain lengths of up to eight amino acid residues. With the enzyme DmpA as the catalyst, we observed very high conversion rates, which correspond to dimer yields of up to 76%. The beta-dipeptide H-beta3 hAla-beta3 hLeu-OH and the beta/alpha-dipeptide H-beta hGly-His-OH (carnosine) were formed with almost 50% conversion, when a five-fold excess of beta3-homoleucine or histidine was incubated with H-beta3 hAla-pNA and H-beta hGly-pNA, respectively, in the presence of the enzyme BapA from S. microcystinivorans Y2. BapA from S. xenopeptidilytica 3-2W4 turned out to be a versatile catalyst capable of coupling various beta-amino acid residues to the free N-termini of beta- and alpha-amino acids and even to an alpha-tripeptide. Thus, these aminopeptidases might be useful to introduce a beta-amino acid residue as an N-terminal protecting group into a 'natural' alpha-peptide, thereby stabilizing the peptide against degradation by other proteolytic enzymes.

  12. 2D 1H and 3D 1H-15N NMR of zinc-rubredoxins: contributions of the beta-sheet to thermostability.

    PubMed Central

    Richie, K. A.; Teng, Q.; Elkin, C. J.; Kurtz, D. M.

    1996-01-01

    Based on 2D 1H-1H and 2D and 3D 1H-15N NMR spectroscopies, complete 1H NMR assignments are reported for zinc-containing Clostridium pasteurianum rubredoxin (Cp ZnRd). Complete 1H NMR assignments are also reported for a mutated Cp ZnRd, in which residues near the N-terminus, namely, Met 1, Lys 2, and Pro 15, have been changed to their counterparts, (-), Ala and Glu, respectively, in rubredoxin from the hyperthermophilic archaeon, Pyrococcus furiosus (Pf Rd). The secondary structure of both wild-type and mutated Cp ZnRds, as determined by NMR methods, is essentially the same. However, the NMR data indicate an extension of the three-stranded beta-sheet in the mutated Cp ZnRd to include the N-terminal Ala residue and Glu 15, as occurs in Pf Rd. The mutated Cp Rd also shows more intense NOE cross peaks, indicating stronger interactions between the strands of the beta-sheet and, in fact, throughout the mutated Rd. However, these stronger interactions do not lead to any significant increase in thermostability, and both the mutated and wild-type Cp Rds are much less thermostable than Pf Rd. These correlations strongly suggest that, contrary to a previous proposal [Blake PR et al., 1992, Protein Sci 1:1508-1521], the thermostabilization mechanism of Pf Rd is not dominated by a unique set of hydrogen bonds or electrostatic interactions involving the N-terminal strand of the beta-sheet. The NMR results also suggest that an overall tighter protein structure does not necessarily lead to increased thermostability. PMID:8732760

  13. Nonlinear evolution of three-dimensional instabilities of thin and thick electron scale current sheets: Plasmoid formation and current filamentation

    SciTech Connect

    Jain, Neeraj; Büchner, Jörg

    2014-07-15

    Nonlinear evolution of three dimensional electron shear flow instabilities of an electron current sheet (ECS) is studied using electron-magnetohydrodynamic simulations. The dependence of the evolution on current sheet thickness is examined. For thin current sheets (half thickness =d{sub e}=c/ω{sub pe}), tearing mode instability dominates. In its nonlinear evolution, it leads to the formation of oblique current channels. Magnetic field lines form 3-D magnetic spirals. Even in the absence of initial guide field, the out-of-reconnection-plane magnetic field generated by the tearing instability itself may play the role of guide field in the growth of secondary finite-guide-field instabilities. For thicker current sheets (half thickness ∼5 d{sub e}), both tearing and non-tearing modes grow. Due to the non-tearing mode, current sheet becomes corrugated in the beginning of the evolution. In this case, tearing mode lets the magnetic field reconnect in the corrugated ECS. Later thick ECS develops filamentary structures and turbulence in which reconnection occurs. This evolution of thick ECS provides an example of reconnection in self-generated turbulence. The power spectra for both the thin and thick current sheets are anisotropic with respect to the electron flow direction. The cascade towards shorter scales occurs preferentially in the direction perpendicular to the electron flow.

  14. Concentration-dependent reversible self-oligomerization of serum albumins through intermolecular β-sheet formation.

    PubMed

    Bhattacharya, Arpan; Prajapati, Roopali; Chatterjee, Surajit; Mukherjee, Tushar Kanti

    2014-12-16

    Proteins inside a cell remain in highly crowded environments, and this often affects their structure and activity. However, most of the earlier studies involving serum albumins were performed under dilute conditions, which lack biological relevance. The effect of protein-protein interactions on the structure and properties of serum albumins at physiological conditions have not yet been explored. Here, we report for the first time the effect of protein-protein and protein-crowder interactions on the structure and stability of two homologous serum albumins, namely, human serum albumin (HSA) and bovine serum albumin (BSA), at physiological conditions by using spectroscopic techniques and scanning electron microscopy (SEM). Concentration-dependent self-oligomerization and subsequent structural alteration of serum albumins have been explored by means of fluorescence and circular dichroism spectroscopy at pH 7.4. The excitation wavelength (λex) dependence of the intrinsic fluorescence and the corresponding excitation spectra at each emission wavelength indicate the presence of various ground state oligomers of serum albumins in the concentration range 10-150 μM. Circular dichroism and thioflavin T binding assay revealed formation of intermolecular β-sheet rich interfaces at high protein concentration. Excellent correlations have been observed between β-sheet content of both the albumins and fluorescence enhancement of ThT with protein concentrations. SEM images at a concentration of 150 μM revealed large dispersed self-oligomeric states with sizes vary from 330 to 924 nm and 260 to 520 nm for BSA and HSA, respectively. The self-oligomerization of serum albumins is found to be a reversible process; upon dilution, these oligomers dissociate into a native monomeric state. It has also been observed that synthetic macromolecular crowder polyethylene glycol (PEG 200) stabilizes the self-associated state of both the albumins which is contrary to expectations that the

  15. Amyloid-beta(29-42) dimer formations studied by a multicanonical-multioverlap molecular dynamics simulation.

    PubMed

    Itoh, Satoru G; Okamoto, Yuko

    2008-03-13

    Amyloid-beta peptides are known to form amyloid fibrils and are considered to play an important role in Alzheimer's disease. Amyloid-beta(29-42) is a fragment of the amyloid-beta peptide and also has a tendency to form amyloid fibrils. In order to study the mechanism of amyloidogenesis of this fragment, we applied one of the generalized-ensemble algorithms, the multicanonical-multioverlap algorithm, to amyloid-beta(29-42) dimer in aqueous solution. We obtained a detailed free-energy landscape of the dimer system. From the detailed free-energy landscape, we examined monomer and dimer formations of amyloid-beta(29-42) and deduced dimerization processes, which correspond to seeding processes in the amyloidogenesis of amyloid-beta(29-42).

  16. Multifunctional acid formation from the gas-phase ozonolysis of beta-pinene.

    PubMed

    Ma, Yan; Marston, George

    2008-10-28

    The gas-phase ozonolysis of beta-pinene was studied in static chamber experiments, using gas chromatography coupled to mass spectrometric and flame ionisation detection to separate and detect products. A range of multifunctional organic acids-including pinic acid, norpinic acid, pinalic-3-acid, pinalic-4-acid, norpinalic acid and OH-pinalic acid-were identified in the condensed phase after derivatisation. Formation yields for these products under systematically varying reaction conditions (by adding different OH radical scavengers and Criegee intermediate scavengers) were investigated and compared with those observed from alpha-pinene ozonolysis, allowing detailed information on product formation mechanisms to be elucidated. In addition, branching ratios for the initial steps of the reaction were inferred from quantitative measurements of primary carbonyl formation. Atmospheric implications of this work are discussed.

  17. Dissecting the structural determinants for the difference in mechanical stability of silk and amyloid beta-sheet stacks.

    PubMed

    Xiao, Senbo; Xiao, Shijun; Gräter, Frauke

    2013-06-14

    Stacking of β-sheets results in a protein super secondary structure with remarkable mechanical properties. β-Stacks are the determinants of a silk fiber's resilience and are also the building blocks of amyloid fibrils. While both silk and amyloid-type crystals are known to feature a high resistance against rupture, their structural and mechanical similarities and particularities are yet to be fully understood. Here, we systematically compare the rupture force and stiffness of amyloid and spider silk poly-alanine β-stacks of comparable sizes using Molecular Dynamics simulations. We identify the direction of force application as the primary determinant of the rupture strength; β-sheets in silk are orientated along the fiber axis, i.e. the pulling direction, and consequently require high forces in the several nanoNewton range for shearing β-strands apart, while β-sheets in amyloid are oriented vertically to the fiber, allowing a zipper-like rupture at sub-nanoNewton forces. A secondary factor rendering amyloid β-stacks softer and weaker than their spider silk counterparts is the sub-optimal side-chain packing between β-sheets due to the sequence variations of amyloid-forming proteins as opposed to the perfectly packed poly-alanine β-sheets of silk. Taken together, amyloid fibers can reach the stiffness of silk fibers in spite of their softer and weaker β-sheet arrangement as they are missing a softening amorphous matrix.

  18. The three-dimensional structural surface of two beta-sheet scorpion toxins mimics that of an alpha-helical dihydropyridine receptor segment.

    PubMed Central

    Green, Daniel; Pace, Suzi; Curtis, Suzanne M; Sakowska, Magdalena; Lamb, Graham D; Dulhunty, Angela F; Casarotto, Marco G

    2003-01-01

    An alpha-helical II-III loop segment of the dihydropyridine receptor activates the ryanodine receptor calcium-release channel. We describe a novel manipulation in which this agonist's activity is increased by modifying its surface structure to resemble that of a toxin molecule. In a unique system, native beta-sheet scorpion toxins have been reported to activate skeletal muscle ryanodine receptor calcium channels with high affinity by binding to the same site as the lower-affinity alpha-helical dihydropyridine receptor segment. We increased the alignment of basic residues in the alpha-helical peptide to mimic the spatial orientation of active residues in the scorpion toxin, with a consequent 2-20-fold increase in the activity of the alpha-helical peptide. We hypothesized that, like the native peptide, the modified peptide and the scorpion toxin may bind to a common site. This was supported by (i) similar changes in ryanodine receptor channel gating induced by the native or modified alpha-helical peptide and the beta-sheet toxin, a 10-100-fold reduction in channel closed time, with a < or = 2-fold increase in open dwell time and (ii) a failure of the toxin to further activate channels activated by the peptides. These results suggest that diverse structural scaffolds can present similar conformational surface properties to target common receptor sites. PMID:12429019

  19. Formation of a very thin current sheet in the near-earth magnetotail and the explosive growth phase of substorms

    NASA Technical Reports Server (NTRS)

    Lee, L. C.; Zhang, L.; Choe, G. S.; Cai, H. J.

    1995-01-01

    A magnetofricional method is used to construct two-dimensional MHD equilibria of the Earth's magnetosphere for a given distribution of entropy functions(S = pV(exp gamma), where p is the plasma pressure and V is the tube volume per unit magnetic flux. It is found that a very thin current sheet with B (sub zeta) is less than 0.5 nu T and thickness less than 1000 km can be formed in the near-earth magnetotail (x is approximately -8 to -20R(sub e) during the growth phase of substorm. The tail current sheets are found to become thinner as the entropy or the entropy gradient increases. It is suggested that the new entropy anti-diffusion instability associated with plasma transport across field lines leads to magnetic field dipolarization and accelerates the formation of thin current sheet, which may explain the observed explosive growth phase of substorms.

  20. Optimal heating condition of mouthguard sheet in vacuum-pressure formation: part 2 Olefin-based thermoplastic elastomer.

    PubMed

    Takahashi, Mutsumi; Koide, Kaoru

    2016-04-01

    The purposes of this study were to clarify the suitable heating conditions during vacuum-pressure formation of olefin copolymer sheets and to examine the sheet temperature at molding and the thickness of the molded mouthguard. Mouthguards were fabricated using 4.0-mm-thick olefin copolymer sheets utilizing a vacuum-pressure forming device, and then, 10 s of vacuum forming and 2 min of compression molding were applied. Three heating conditions were investigated. They were, defined by the degree of sagging observed at the center of the softened sheet (10, 15, or 20 mm lower than the clamp (H-10, H-15, or H-20, respectively)). The working model was trimmed to the height of 20 mm at the maxillary central incisor and 15 mm at the mesiobuccal cusp of the maxillary first molar. The temperature on both the directly heated and the non-heated surfaces of the mouthguard sheet was measured by the radiation thermometer for each condition. The thickness of mouthguard sheets after fabrication was determined for the incisal portion (incisal edge and labial surface) and molar portion (cusp and buccal surface), and dimensional measurements were obtained using a measuring device. Differences in the thickness due to the heating condition of the sheets were analyzed by one-way analysis of variance and Bonferroni's multiple comparison tests. The temperature difference between the heated and non-heated surfaces was highest under H-10. Sheet temperature under H-15 and H-20 was almost the same. The thickness differences were noted at incisal edge, cusp, and buccal surface, and H-15 was the greatest. This study demonstrated that heating of the sheet resulting in sag of 15 mm or more was necessary for sufficient softening of the sheet and that the mouthguard thickness decreased with increased sag. In conclusion, sag of 15 mm can be recommended as a good indicator of appropriate molding timing for this material.

  1. Protein Secondary Structures (alpha-helix and beta-sheet) at a Cellular Levle and Protein Fractions in Relation to Rumen Degradation Behaviours of Protein: A New Approach

    SciTech Connect

    Yu,P.

    2007-01-01

    Studying the secondary structure of proteins leads to an understanding of the components that make up a whole protein, and such an understanding of the structure of the whole protein is often vital to understanding its digestive behaviour and nutritive value in animals. The main protein secondary structures are the {alpha}-helix and {beta}-sheet. The percentage of these two structures in protein secondary structures influences protein nutritive value, quality and digestive behaviour. A high percentage of {beta}-sheet structure may partly cause a low access to gastrointestinal digestive enzymes, which results in a low protein value. The objectives of the present study were to use advanced synchrotron-based Fourier transform IR (S-FTIR) microspectroscopy as a new approach to reveal the molecular chemistry of the protein secondary structures of feed tissues affected by heat-processing within intact tissue at a cellular level, and to quantify protein secondary structures using multicomponent peak modelling Gaussian and Lorentzian methods, in relation to protein digestive behaviours and nutritive value in the rumen, which was determined using the Cornell Net Carbohydrate Protein System. The synchrotron-based molecular chemistry research experiment was performed at the National Synchrotron Light Source at Brookhaven National Laboratory, US Department of Energy. The results showed that, with S-FTIR microspectroscopy, the molecular chemistry, ultrastructural chemical make-up and nutritive characteristics could be revealed at a high ultraspatial resolution ({approx}10 {mu}m). S-FTIR microspectroscopy revealed that the secondary structure of protein differed between raw and roasted golden flaxseeds in terms of the percentages and ratio of {alpha}-helixes and {beta}-sheets in the mid-IR range at the cellular level. By using multicomponent peak modelling, the results show that the roasting reduced (P <0.05) the percentage of {alpha}-helixes (from 47.1% to 36.1%: S

  2. Repetitive formation and decay of current sheets in magnetic loops: An origin of diverse magnetic structures

    NASA Astrophysics Data System (ADS)

    Kumar, Dinesh; Bhattacharyya, R.; Smolarkiewicz, P. K.

    2015-01-01

    In this work, evolution of an incompressible, thermally homogeneous, infinitely conducting, viscous magnetofluid is numerically explored as the fluid undergoes repeated events of magnetic reconnection. The initial magnetic field is constructed by a superposition of two linear force-free fields and has similar morphology as the magnetic loops observed in the solar corona. The results are presented for computations with three distinct sets of footpoint geometries. To onset reconnection, we rely on numerical model magnetic diffusivity, in the spirit of implicit large eddy simulation. It is generally expected that in a high Lundquist number fluid, repeated magnetic reconnections are ubiquitous and hence can lead to a host of magnetic structures with considerable observational importance. In particular, the simulations presented here illustrate formations of magnetic islands, rotating magnetic helices and rising flux ropes—depending on the initial footpoint geometry but through the common process of repeated magnetic reconnections. Further, we observe the development of extended current sheets in two case studies, where the footpoint reconnections generate favorable dynamics.

  3. Repetitive formation and decay of current sheets in magnetic loops: An origin of diverse magnetic structures

    SciTech Connect

    Kumar, Dinesh; Bhattacharyya, R.; Smolarkiewicz, P. K.

    2015-01-15

    In this work, evolution of an incompressible, thermally homogeneous, infinitely conducting, viscous magnetofluid is numerically explored as the fluid undergoes repeated events of magnetic reconnection. The initial magnetic field is constructed by a superposition of two linear force-free fields and has similar morphology as the magnetic loops observed in the solar corona. The results are presented for computations with three distinct sets of footpoint geometries. To onset reconnection, we rely on numerical model magnetic diffusivity, in the spirit of implicit large eddy simulation. It is generally expected that in a high Lundquist number fluid, repeated magnetic reconnections are ubiquitous and hence can lead to a host of magnetic structures with considerable observational importance. In particular, the simulations presented here illustrate formations of magnetic islands, rotating magnetic helices and rising flux ropes—depending on the initial footpoint geometry but through the common process of repeated magnetic reconnections. Further, we observe the development of extended current sheets in two case studies, where the footpoint reconnections generate favorable dynamics.

  4. Inducing β-sheets formation in synthetic spider silk fibers by aqueous post-spin stretching.

    PubMed

    An, Bo; Hinman, Michael B; Holland, Gregory P; Yarger, Jeffery L; Lewis, Randolph V

    2011-06-13

    As a promising biomaterial with numerous potential applications, various types of synthetic spider silk fibers have been produced and studied in an effort to produce man-made fibers with mechanical and physical properties comparable to those of native spider silk. In this study, two recombinant proteins based on Nephila clavipes Major ampullate Spidroin 1 (MaSp1) consensus repeat sequence were expressed and spun into fibers. Mechanical test results showed that fiber spun from the higher molecular weight protein had better overall mechanical properties (70 KD versus 46 KD), whereas postspin stretch treatment in water helped increase fiber tensile strength significantly. Carbon-13 solid-state NMR studies of those fibers further revealed that the postspin stretch in water promoted protein molecule rearrangement and the formation of β-sheets in the polyalanine region of the silk. The rearrangement correlated with improved fiber mechanical properties and indicated that postspin stretch is key to helping the spider silk proteins in the fiber form correct secondary structures, leading to better quality fibers. PMID:21574576

  5. Metabolism of cholesteryl palmitate by rat brain in vitro; formation of cholesterol epoxides and cholestane-3beta,5alpha,6beta-triol.

    PubMed

    Martin, C M; Nicholas, H J

    1973-11-01

    Incubation of [4-(14)C]cholesteryl palmitate with the 12,000 g supernatant fraction of adult rat brain fortified with an NADPH-generating system and beta-mercaptoethylamine resulted in formation (2-5%) of more polar metabolites characterized as a mixture of cholesterol-5,6-epoxides. Under extended incubation conditions, cholestane-3beta-5alpha-6beta-triol was isolated as the major end product of the incubations. Free [4-(14)C]cholesterol incubated under similar conditions was not oxidized, whereas oxidation of [4-(14)C]cholesteryl palmitate appeared to be dependent upon hydrolysis of the ester by the rat brain microsomal subcellular fraction. Elimination of the NADPH-generating system or the addition of EDTA to the incubation mixture inhibited epoxide formation, suggesting that the products are derived from an NADPH-dependent enzymatic lipoperoxidation mechanism. The in vitro conversion of [4-(14)C]cholesterol-5alpha,6alpha-epoxide to cholestane-3beta,5alpha,6beta-triol was also demonstrated in rat brain subcellular fractions in the absence of added cofactors.

  6. Rapid Ti(III) reduction of perchlorate in the presence of beta-alanine: kinetics, pH effect, complex formation, and beta-alanine effect.

    PubMed

    Wang, Chao; Huang, Zhengdao; Lippincott, Lee; Meng, Xiaoguang

    2010-03-15

    Ti(III) reduction of perchlorate might be a useful method for the treatment of highly perchlorate-contaminated water. Though the reaction rate was usually low, we observed that beta-alanine (HOOCCH(2)CH(2)NH(2)) could significantly promote the reaction. A complete (>99.9%) perchlorate removal was obtained in a solution containing [ClO(4)(-)]=1.0mM, [Ti(III)]=40 mM, and [beta-alanine]=120 mM after 2.5h of reaction under 50 degrees C. The effects of both pH and complex formation on the reaction were then studied. The results showed that without beta-alanine the optimal pH was 2.3. When pH increased from 1.6 to 2.3, the reduction rate increased remarkably. In the pH range >2.3, however, the reduction was significantly inhibited, attributed to the formation of Ti(III) precipitate. The presence of beta-alanine at a molar ratio of [beta-alanine]:[Ti(III)]=3:1 significantly increased the reduction rate of perchlorate even at near neutral pH. This is because beta-alanine formed complexes with Ti(III), which greatly improved the total soluble [Ti(III)] in the pH range between 3.5 and 6. The findings may lead to the development of rapid treatment methods for intermittent and small stream of highly perchlorate-contaminated water, which are resulted from the manufacturing, storage, handling, use and/or disposal of large quantities of perchlorate salts. PMID:19864064

  7. Rapid Ti(III) reduction of perchlorate in the presence of beta-alanine: kinetics, pH effect, complex formation, and beta-alanine effect.

    PubMed

    Wang, Chao; Huang, Zhengdao; Lippincott, Lee; Meng, Xiaoguang

    2010-03-15

    Ti(III) reduction of perchlorate might be a useful method for the treatment of highly perchlorate-contaminated water. Though the reaction rate was usually low, we observed that beta-alanine (HOOCCH(2)CH(2)NH(2)) could significantly promote the reaction. A complete (>99.9%) perchlorate removal was obtained in a solution containing [ClO(4)(-)]=1.0mM, [Ti(III)]=40 mM, and [beta-alanine]=120 mM after 2.5h of reaction under 50 degrees C. The effects of both pH and complex formation on the reaction were then studied. The results showed that without beta-alanine the optimal pH was 2.3. When pH increased from 1.6 to 2.3, the reduction rate increased remarkably. In the pH range >2.3, however, the reduction was significantly inhibited, attributed to the formation of Ti(III) precipitate. The presence of beta-alanine at a molar ratio of [beta-alanine]:[Ti(III)]=3:1 significantly increased the reduction rate of perchlorate even at near neutral pH. This is because beta-alanine formed complexes with Ti(III), which greatly improved the total soluble [Ti(III)] in the pH range between 3.5 and 6. The findings may lead to the development of rapid treatment methods for intermittent and small stream of highly perchlorate-contaminated water, which are resulted from the manufacturing, storage, handling, use and/or disposal of large quantities of perchlorate salts.

  8. Spontaneous formation of stringlike clusters and smectic sheets for colloidal rods confined in thin wedgelike gaps.

    PubMed

    Maeda, Hideatsu; Maeda, Yoshiko

    2013-08-20

    Monodispersed colloidal rods of β-FeOOH with sizes ranging from 270 to 580 nm in length and 50 to 80 nm in width were synthesized. Narrow wedgelike gaps (0 to 700 nm in height) were formed around the inner bottom edge of the suspension glass cells. Optical microscopic observations revealed the formation of stringlike clusters of the rods and smectic sheets (by spontaneous side-by-side clustering of the strings) in the isotropic phase of the rod suspensions confined in narrow gaps; the electrolyte (HCl) concentrations of the suspensions are 5-40 mM, at which inter-rod interactions are attractive. The strings exhibit different colors that were used to investigate the structures of the strings with the help of interference color theory for thin films. The results are as follows. (1) The rods, lying flat on the gap bottom, are connected side-by-side and stacked upward to form stringlike clusters with different thicknesses depending on the gap height. (2) The stacking numbers (N(sr)) of the rods are estimated to be 1-5. With N(sr) increasing from 2 to 5, the volume fractions (ϕ) of the rods in the strings increased typically from 0.25-0.3 to 0.35-0.42 to reach limiting values (close to the ϕ values of the rods in the bulk smectic phase). (3) Unexpected low-ϕ strings are found in regions with an intermediate height in the gaps. These behaviors of ϕ may be caused by thermal fluctuations of the strings.

  9. Spontaneous formation of stringlike clusters and smectic sheets for colloidal rods confined in thin wedgelike gaps.

    PubMed

    Maeda, Hideatsu; Maeda, Yoshiko

    2013-08-20

    Monodispersed colloidal rods of β-FeOOH with sizes ranging from 270 to 580 nm in length and 50 to 80 nm in width were synthesized. Narrow wedgelike gaps (0 to 700 nm in height) were formed around the inner bottom edge of the suspension glass cells. Optical microscopic observations revealed the formation of stringlike clusters of the rods and smectic sheets (by spontaneous side-by-side clustering of the strings) in the isotropic phase of the rod suspensions confined in narrow gaps; the electrolyte (HCl) concentrations of the suspensions are 5-40 mM, at which inter-rod interactions are attractive. The strings exhibit different colors that were used to investigate the structures of the strings with the help of interference color theory for thin films. The results are as follows. (1) The rods, lying flat on the gap bottom, are connected side-by-side and stacked upward to form stringlike clusters with different thicknesses depending on the gap height. (2) The stacking numbers (N(sr)) of the rods are estimated to be 1-5. With N(sr) increasing from 2 to 5, the volume fractions (ϕ) of the rods in the strings increased typically from 0.25-0.3 to 0.35-0.42 to reach limiting values (close to the ϕ values of the rods in the bulk smectic phase). (3) Unexpected low-ϕ strings are found in regions with an intermediate height in the gaps. These behaviors of ϕ may be caused by thermal fluctuations of the strings. PMID:23876087

  10. Inhibitory effects of nisin-coated multi-walled carbon nanotube sheet on biofilm formation from Bacillus anthracis spores.

    PubMed

    Dong, Xiuli; McCoy, Eric; Zhang, Mei; Yang, Liju

    2014-12-01

    Multi-walled carbon nanotube (MWCNT) sheet was fabricated from a drawable MWCNT forest and then deposited on poly(methyl methacrylate) film. The film was further coated with a natural antimicrobial peptide nisin. We studied the effects of nisin coating on the attachment of Bacillus anthracis spores, the germination of attached spores, and the subsequent biofilm formation from attached spores. It was found that the strong adsorptivity and the super hydrophobicity of MWCNTs provided an ideal platform for nisin coating. Nisin coating on MWCNT sheets decreased surface hydrophobicity, reduced spore attachment, and reduced the germination of attached spores by 3.5 fold, and further inhibited the subsequent biofilm formation by 94.6% compared to that on uncoated MWCNT sheet. Nisin also changed the morphology of vegetative cells in the formed biofilm. The results of this study demonstrated that the anti-adhesion and antimicrobial effect of nisin in combination with the physical properties of carbon nanotubes had the potential in producing effective anti-biofilm formation surfaces.

  11. Coordination of chondrocyte differentiation and joint formation by alpha5beta1 integrin in the developing appendicular skeleton.

    PubMed

    Garciadiego-Cázares, David; Rosales, Carlos; Katoh, Masaru; Chimal-Monroy, Jesús

    2004-10-01

    The control point by which chondrocytes take the decision between the cartilage differentiation program or the joint formation program is unknown. Here, we have investigated the effect of alpha5beta1 integrin inhibitors and bone morphogenetic protein (BMP) on joint formation. Blocking of alpha5beta1 integrin by specific antibodies or RGD peptide (arginine-glycine-aspartic acid) induced inhibition of pre-hypertrophic chondrocyte differentiation and ectopic joint formation between proliferating chondrocytes and hypertrophic chondrocytes. Ectopic joint expressed Wnt14, Gdf5, chordin, autotaxin, type I collagen and CD44, while expression of Indian hedgehog and type II collagen was downregulated in cartilage. Expression of these interzone markers confirmed that the new structure is a new joint being formed. In the presence of BMP7, inhibition of alpha5beta1 integrin function still induced the formation of the ectopic joint between proliferating chondrocytes and hypertrophic chondrocytes. By contrast, misexpression of alpha5beta1 integrin resulted in fusion of joints and formation of pre-hypertrophic chondrocytes. These facts indicate that the decision of which cell fate to make pre-joint or pre-hypertrophic is made on the basis of the presence or absence of alpha5beta1 integrin on chondrocytes.

  12. Formation of fusarenone X, nivalenol, zearalenone, alpha-trans-zearalenol, beta-trans-zearalenol, and fusarin C by Fusarium crookwellense.

    PubMed

    Golinski, P; Vesonder, R F; Latus-Zietkiewicz, D; Perkowski, J

    1988-08-01

    Fusarium crookwellense KF748 (NRRL A-28100) (isolated from dry rotted potato tubers in Central Poland) produced six mycotoxins on both rice and corn substrates at 25 degrees C. The metabolites detected were zearalenone, alpha-trans-zearalenol, beta-trans-zearalenol, fusarin C, and the trichothecenes fusarenone X and nivalenol. This is the first report of formation of alpha-trans-zearalenol, beta-trans-zearalenol, fusarenone X, and nivalenol by F. crookwellense.

  13. A study of the formation and dynamics of the Earth's plasma sheet using ion composition data

    NASA Technical Reports Server (NTRS)

    Lennartsson, O. W.

    1994-01-01

    Over two years of data from the Lockheed Plasma Composition Experiment on the ISEE 1 spacecraft, covering ion energies between 100 eV/e and about 16 keV/e, have been analyzed in an attempt to extract new information about three geophysical issues: (1) solar wind penetration of the Earth's magnetic tail; (2) relationship between plasma sheet and tail lobe ion composition; and (3) possible effects of heavy terrestrial ions on plasma sheet stability.

  14. Differential mode of interaction of ThioflavinT with native β structural motif in human α 1-acid glycoprotein and cross beta sheet of its amyloid: Biophysical and molecular docking approach

    NASA Astrophysics Data System (ADS)

    Ajmal, Mohammad Rehan; Nusrat, Saima; Alam, Parvez; Zaidi, Nida; Badr, Gamal; Mahmoud, Mohamed H.; Rajpoot, Ravi Kant; Khan, Rizwan Hasan

    2016-08-01

    The present study details the interaction mechanism of Thioflavin T (ThT) to Human α1-acid glycoprotein (AAG) applying various spectroscopic and molecular docking methods. Fluorescence quenching data revealed the binding constant in the order of 104 M-1 and the standard Gibbs free energy change value, ΔG = -6.78 kcal mol-1 for the interaction between ThT and AAG indicating process is spontaneous. There is increase in absorbance of AAG upon the interaction of ThT that may be due to ground state complex formation between ThT and AAG. ThT impelled rise in β-sheet structure in AAG as observed from far-UV CD spectra while there are minimal changes in tertiary structure of the protein. DLS results suggested the reduction in AAG molecular size, ligand entry into the central binding pocket of AAG may have persuaded the molecular compaction in AAG. Isothermal titration calorimetric (ITC) results showed the interaction process to be endothermic with the values of standard enthalpy change ΔH0 = 4.11 kcal mol-1 and entropy change TΔS0 = 10.82 kcal.mol- 1. Moreover, docking results suggested hydrophobic interactions and hydrogen bonding played the important role in the binding process of ThT with F1S and A forms of AAG. ThT fluorescence emission at 485 nm was measured for properly folded native form and for thermally induced amyloid state of AAG. ThT fluorescence with native AAG was very low, while on the other hand with amyloid induced state of the protein AAG showed a positive emission peak at 485 nm upon the excitation at 440 nm, although it binds to native state as well. These results confirmed that ThT binding alone is not responsible for enhancement of ThT fluorescence but it also required beta stacked sheet structure found in protein amyloid to give proper signature signal for amyloid. This study gives the mechanistic insight into the differential interaction of ThT with beta structures found in native state of the proteins and amyloid forms, this study reinforce

  15. Diagnostics of basal conditions - the formation of extensive zones of surface ribs in ice-sheets and streams

    NASA Astrophysics Data System (ADS)

    Hindmarsh, Richard C. A.; Sergienko, Olga V.; Creyts, Timothy T.

    2015-04-01

    Most if not all current predictions of the evolution of ice-streams to changes induced by global change assume static basal conditions. This is a result of current restrictions in the remote sensing of the ice-sheet basal physical environment, which cannot resolve the small-scale phenomena believed to control the basal traction. The search therefore is on for observable structures or features that are the result of the operation of basal processes. Any successful theory of ice-sheet basal processes would need to be able to explain such phenomena associated with or caused by special properties of the basal environment. We present one class of these phenomena, and also present tentative hypotheses as to their formation. Using recent high-resolution observations of the Antarctic and Greenland ice sheets topography, the computed driving stress and the inferred basal traction reveal broad-scale organization in 5-20 km band-like patterns in both quantities. The similarity of patterns on the Greenland and Antarctic ice sheets suggests that the flow of ice sheets is controlled by the same fundamental processes operating at their base, which control ice sheet sliding and are highly variable on relatively short spatial and temporal scales. The formation mechanism for these bands contains information about the operation of the sub-glacial system. There are three possible, non-exclusive causes of these ribs which we examine from a theoretical and evidential point-of-view (i) They are the surface response to similar bands in the basal topography, whose regularity would equally require an explanation in terms of basal processes. (ii) They are translating surface waves in the ice, supported by membrane stress gradients rather than by gradients in the basal resistance. (iii) The ribs are due to the development of a band-like structure in the basal shear stress distribution that is the result of a pattern-forming instability in sub-glacial till and water flow, perhaps related to

  16. A folding pathway for betapep-4 peptide 33mer: from unfolded monomers and beta-sheet sandwich dimers to well-structured tetramers.

    PubMed

    Mayo, K H; Ilyina, E

    1998-02-01

    It was recently reported that a de novo designed peptide 33mer, betapep-4, can form well-structured beta-sheet sandwich tetramers (Ilyina E, Roongta V, Mayo KH, 1997b, Biochemistry 36:5245-5250). For insight into the pathway of betapep-4 folding, the present study investigates the concentration dependence of betapep-4 self-association by using 1H-NMR pulsed-field gradient (PFG)-NMR diffusion measurements, and circular dichroism. Downfield chemically shifted alphaH resonances, found to arise only from the well-structured betapep-4 tetramer state, yield the fraction of tetramer within the oligomer equilibrium distribution. PFG-NMR-derived diffusion coefficients, D, provide a means for deriving the contribution of monomer and other oligomer states to this distribution. These data indicate that tetramer is the highest oligomer state formed, and that inclusion of monomer and dimer states in the oligomer distribution is sufficient to explain the concentration dependence of D values for betapep-4. Equilibrium constants calculated from these distributions [2.5 x 10(5) M(-1) for M-D and 1.2 x 10(4) M(-1) for D-T at 313 K] decrease only slightly, if at all, with decreasing temperature indicating a hydrophobically mediated, entropy-driven association/folding process. Conformational analyses using NMR and CD provide a picture where "random coil" monomers associate to form molten globule-like beta-sheet sandwich dimers that further associate and fold as well-structured tetramers. Betapep-4 folding is thermodynamically linked to self-association. As with folding of single-chain polypeptides, the final folding step to well-structured tetramer betapep-4 is rate limiting.

  17. Embryonic neural inducing factor churchill is not a DNA-binding zinc finger protein: solution structure reveals a solvent-exposed beta-sheet and zinc binuclear cluster.

    PubMed

    Lee, Brian M; Buck-Koehntop, Bethany A; Martinez-Yamout, Maria A; Dyson, H Jane; Wright, Peter E

    2007-08-31

    Churchill is a zinc-containing protein that is involved in neural induction during embryogenesis. At the time of its discovery, it was thought on the basis of sequence alignment to contain two zinc fingers of the C4 type. Further, binding of an N-terminal GST-Churchill fusion protein to a particular DNA sequence was demonstrated by immunoprecipitation selection assay, suggesting that Churchill may function as a transcriptional regulator by sequence-specific DNA binding. We show by NMR solution structure determination that, far from containing canonical C4 zinc fingers, the protein contains three bound zinc ions in novel coordination sites, including an unusual binuclear zinc cluster. The secondary structure of Churchill is also unusual, consisting of a highly solvent-exposed single-layer beta-sheet. Hydrogen-deuterium exchange and backbone relaxation measurements reveal that Churchill is unusually dynamic on a number of time scales, with the exception of regions surrounding the zinc coordinating sites, which serve to stabilize the otherwise unstructured N terminus and the single-layer beta-sheet. No binding of Churchill to the previously identified DNA sequence could be detected, and extensive searches using DNA sequence selection techniques could find no other DNA sequence that was bound by Churchill. Since the N-terminal amino acids of Churchill form part of the zinc-binding motif, the addition of a fusion protein at the N terminus causes loss of zinc and unfolding of Churchill. This observation most likely explains the published DNA-binding results, which would arise due to non-specific interaction of the unfolded protein in the immunoprecipitation selection assay. Since Churchill does not appear to bind DNA, we suggest that it may function in embryogenesis as a protein-interaction factor.

  18. The effect of low levels of dopants upon the formation and properties of beta-phase molybdenum nitride

    SciTech Connect

    Cairns, A.G.; Gallagher, J.G.; Hargreaves, J.S.J.; Mckay, D.; Rico, J.L.; Wilson, K.

    2010-03-15

    The addition of 1 wt% Pd, Au, Ni and Cu dopants has been demonstrated to strongly alter the morphology of beta-phase molybdenum nitride prepared by treatment of MoO{sub 3} with a 3/1 H{sub 2}/N{sub 2} mixture at 750 deg. C. Furthermore, the addition of Pd significantly enhances the surface area and the formation of the nitride phase. It is proposed that the facile formation of molybdenum bronzes in this system is important in this respect. The dopants have also been observed to modify the denitridation characteristics of the beta-phase, with an overall reduction of the proportion of NH{sub 3} formed upon using a 3/1 H{sub 2}/Ar mixture with respect to the undoped sample. - Graphical abstract: Low levels of Pd, Au, Ni and Cu dopant have significant effects upon the morphology, formation and dentitridation characteristics of beta-phase molybdenum nitride.

  19. Current sheet formation in a sheared force-free-magnetic field. [in sun

    NASA Technical Reports Server (NTRS)

    Wolfson, Richard

    1989-01-01

    This paper presents the results of a study showing how continuous shearing motion of magnetic footpoints in a tenuous, infinitely conducting plasma can lead to the development of current sheets, despite the absence of such sheets or even of neutral points in the initial state. The calculations discussed here verify the earlier suggestion by Low and Wolfson (1988) that extended current sheets should form due to the shearing of a force-free quadrupolar magnetic field. More generally, this work augments earlier studies suggesting that the appearance of discontinuities - current sheets - may be a necessary consequence of the topological invariance imposed on the magnetic field geometry of an ideal MHD system by virtue of its infinite conductivity. In the context of solar physics, the work shows how the gradual and continuous motion of magnetic footpoints at the solar photosphere may lead to the buildup of magnetic energy that can then be released explosively when finite conductivity effects become important and lead to the rapid dissipation of current sheets. Such energy release may be important in solar flares, coronal mass ejections, and other eruptive events.

  20. Solvent effects on self-assembly of beta-amyloid peptide.

    PubMed Central

    Shen, C L; Murphy, R M

    1995-01-01

    beta-amyloid peptide (A beta) is the primary protein component of senile plaques in Alzheimer's disease patients. Synthetic A beta spontaneously assembles into amyloid fibrils and is neurotoxic to cortical cultures. Neurotoxicity has been associated with the degree of peptide aggregation, yet the mechanism of assembly of A beta into amyloid fibrils is poorly understood. In this work, A beta was dissolved in several different solvents commonly used in neurotoxicity assays. In pure dimethylsulfoxide (DMSO), A beta had no detectable beta-sheet content; in 0.1% trifluoroacetate, the peptide contained one-third beta-sheet; and in 35% acetonitrile/0.1% trifluoroacetate, A beta was two-thirds beta-sheet, equivalent to the fibrillar peptide in physiological buffer. Stock solutions of peptide were diluted into phosphate-buffered saline, and fibril growth was followed by static and dynamic light scattering. The growth rate was substantially faster when the peptide was predissolved in 35% acetonitrile/0.1% trifluoroacetate than in 0.1% trifluoroacetate, 10% DMSO, or 100% DMSO. Differences in growth rate were attributed to changes in the secondary structure of the peptide in the stock solvent. These results suggest that formation of an intermediate with a high beta-sheet content is a controlling step in A beta self-assembly. PMID:8527678

  1. Doubling the cross-linking interface of a rationally designed beta roll peptide for calcium-dependent proteinaceous hydrogel formation.

    PubMed

    Dooley, Kevin; Bulutoglu, Beyza; Banta, Scott

    2014-10-13

    We have rationally engineered a stimulus-responsive cross-linking domain based on a repeats-in-toxin (RTX) peptide to enable calcium-dependent formation of supramolecular hydrogel networks. The peptide isolated from the RTX domain is intrinsically disordered in the absence of calcium. In calcium rich environments, the peptide binds Ca(2+) ions and folds into a beta roll (β-roll) secondary structure composed to two parallel β-sheet faces. Previously, we mutated one of the faces to contain solvent exposed leucine side chains which are localized only in the calcium-bound β-roll conformation. We demonstrated the ability of this mutant peptide to self-assemble into hydrogels in the presence of calcium with the aid of additional peptide-based cross-linking moieties. Here, we have expanded this approach by engineering both β-roll faces to contain leucine residues, thereby doubling the cross-linking interface for each monomeric building block. These leucine rich surfaces impart a hydrophobic driving force for self-assembly. Extensive characterization was performed on this double-faced mutant to ensure the retention of calcium affinity and subsequent structural rearrangement similar to that of the wild type domain. We genetically fused an α-helical leucine zipper capable of forming tetrameric coiled-coil bundles to the peptide and the resulting chimeric protein self-assembles into a hydrogel only in calcium rich environments. Since this new mutant peptide enables cross-linking on both surfaces simultaneously, a higher oligomerization state was achieved. To further investigate the cross-linking capability, we constructed concatemers of the β-roll with maltose binding protein (MBP), a monomeric globular protein, without the leucine zipper domains. These concatemers show a similar sol-gel transition in response to calcium. Several biophysical techniques were used to probe the structural and mechanical properties of the mutant β-roll domain and the resulting

  2. Double-stranded helical twisted beta-sheet channels in crystals of gramicidin S grown in the presence of trifluoroacetic and hydrochloric acids.

    PubMed

    Llamas-Saiz, Antonio L; Grotenbreg, Gijsbert M; Overhand, Mark; van Raaij, Mark J

    2007-03-01

    Gramicidin S is a nonribosomally synthesized cyclic decapeptide antibiotic with twofold symmetry (Val-Orn-Leu-D-Phe-Pro)(2); a natural source is Bacillus brevis. Gramicidin S is active against Gram-positive and some Gram-negative bacteria. However, its haemolytic toxicity in humans limits its use as an antibiotic to certain topical applications. Synthetically obtained gramicidin S was crystallized from a solution containing water, methanol, trifluoroacetic acid and hydrochloric acid. The structure was solved and refined at 0.95 A resolution. The asymmetric unit contains 1.5 molecules of gramicidin S, two trifluoroacetic acid molecules and ten water molecules located and refined in 14 positions. One gramicidin S molecule has an exact twofold-symmetrical conformation; the other deviates from the molecular twofold symmetry. The cyclic peptide adopts an antiparallel beta-sheet secondary structure with two type II' beta-turns. These turns have the residues D-Phe and Pro at positions i + 1 and i + 2, respectively. In the crystals, the gramicidin S molecules line up into double-stranded helical channels that differ from those observed previously. The implications of the supramolecular structure for several models of gramicidin S conformation and assembly in the membrane are discussed.

  3. Numerical model of meltwater retention and firn aquifer formation in Greenland Ice Sheet

    NASA Astrophysics Data System (ADS)

    Liu, X.; Bassis, J. N.

    2014-12-01

    Observations show increasing surface melt and mass loss from the Greenland ice sheet. However, at present considerable uncertainty remains in understanding and predicting, much of the meltwater produced is retained and how much reaches the ocean through surface runoff or by draining through moulins. The potential for the Greenland ice sheet to retain substantial amounts of water has been highlighted by the recent and surprising discovery of a semi-permanent firn aquifer. In this study, we use a numerical model to simulate surface melt and track the meltwater evolution in the snow and firn layer to explore how the firn aquifer forms and their influence on Greenland Ice Sheet mass balance and dynamics. The model is coupled with a surface energy balance model, which computes surface energy and mass balance processes, and a snow-firn model, which simulates snow and ice metamorphic processes and englacial water transport processes. Case studies were carried on the melting part of Greenland Ice Sheet to calibrate and validate the model, driven by in situ AWS stations observational data and ERA-interim downscaled reanalysis data. Model results are used to analyze the conditions on which firn aquifer forms and examine limitations associated with driving a model with coarse scale climate data. We also examine the sensitivity to model results to different parameterization of albedo, densification and water transport.

  4. Inhibition of bacterial cell wall-induced leukocyte recruitment and hepatic granuloma formation by TGF-beta gene transfer.

    PubMed

    Song, X; Zeng, L; Pilo, C M; Zagorski, J; Wahl, S M

    1999-10-01

    Intraperitoneal injection of streptococcal cell walls (SCW) into Lewis rats results in dissemination of SCW to the liver, spleen, bone marrow, and peripheral joints. The uptake of SCW by Kupffer cells in the liver initiates a chain of events largely mediated by T lymphocytes and macrophages. Local synthesis and secretion of cytokines and growth factors in response to the persistent SCW lead to the evolution and maintenance of a chronic T cell-dependent granulomatous response and result in granuloma formation and irreversible hepatic fibrosis. In an attempt to impede the development of the chronic granulomatous lesions in the liver, we injected a plasmid DNA encoding TGF-beta 1 i.m. to the SCW animals to determine the effect of TGF-beta 1 gene transfer on the course of liver inflammation and fibrosis. A single injection of plasmid DNA encoding TGF-beta 1 resulted in virtual abolition of the development of the SCW-induced hepatic granuloma formation and matrix expansion. TGF-beta 1 DNA not only reduced key proinflammatory cytokines including TNF-alpha, IL-1 beta, IFN-gamma, and IL-18, but also inhibited both CXC and CC chemokine production, thereby blocking inflammatory cell recruitment and accumulation in the liver. Moreover, TGF-beta 1 gene delivery inhibited its own expression in the liver tissue, which is otherwise up-regulated in SCW-injected animals. Our study suggests that TGF-beta 1 gene transfer suppresses hepatic granuloma formation by blocking the recruitment of inflammatory cells to the liver, and thus may provide a new approach to the control of hepatic granulomatous and fibrotic diseases. PMID:10491005

  5. Experimental study of bone formation around a titanium rod with beta-tricalcium phosphate and prostaglandin E2 receptor agonists.

    PubMed

    Masuzawa, Michinaga; Beppu, Moroe; Ishii, Shoji; Oyake, Yuichiro; Aoki, Haruhito; Takagi, Masayuki

    2005-05-01

    beta-Tricalcium phosphate (beta-TCP) is an excellent bone-filling material that is completely absorbed by the body and replaced by autologous bone. Unfortunately, its mechanical strength is low, rendering its application at loaded regions difficult. The purpose of this study is to evaluate the histological and mechanical effects of single and combined use of beta-TCP and EP4 agonist on bone formation around a titanium rod. beta-TCP was loaded into the femoral bone marrow from the distal end of the femur, where the titanium implants were inserted, and the animals received twice-daily subcutaneous injections of EP4 agonist. Group I received the rod only and was designated the control group; group II received EP4 agonist only; group III received beta-TCP only; and group IV received both beta-TCP and EP4 agonist. Examination of decalcified specimens revealed favorable bone formation in all treatment groups compared with that in group I, with the most active bone formation seen in group IV. Mechanical evaluation revealed significant differences in maximum pull-out force compared with group I at weeks 4 and 8. There were no differences between groups II and III at either week 4 or 8, but the values seen in group IV at weeks 4 and 8 were significantly higher compared with the other groups. Combined use of beta-TCP and EP4 agonist is expected to compensate for bone defects resulting from revision total joint arthroplasty and to achieve stability at an early stage. PMID:15928895

  6. Effects of Transforming Growth Factor Beta 1 in Cerebellar Development: Role in Synapse Formation

    PubMed Central

    Araujo, Ana P. B.; Diniz, Luan P.; Eller, Cristiane M.; de Matos, Beatriz G.; Martinez, Rodrigo; Gomes, Flávia C. A.

    2016-01-01

    Granule cells (GC) are the most numerous glutamatergic neurons in the cerebellar cortex and represent almost half of the neurons of the central nervous system. Despite recent advances, the mechanisms of how the glutamatergic synapses are formed in the cerebellum remain unclear. Among the TGF-β family, TGF-beta 1 (TGF-β1) has been described as a synaptogenic molecule in invertebrates and in the vertebrate peripheral nervous system. A recent paper from our group demonstrated that TGF-β1 increases the excitatory synapse formation in cortical neurons. Here, we investigated the role of TGF-β1 in glutamatergic cerebellar neurons. We showed that the expression profile of TGF-β1 and its receptor, TβRII, in the cerebellum is consistent with a role in synapse formation in vitro and in vivo. It is low in the early postnatal days (P1–P9), increases after postnatal day 12 (P12), and remains high until adulthood (P30). We also found that granule neurons express the TGF-β receptor mRNA and protein, suggesting that they may be responsive to the synaptogenic effect of TGF-β1. Treatment of granular cell cultures with TGF-β1 increased the number of glutamatergic excitatory synapses by 100%, as shown by immunocytochemistry assays for presynaptic (synaptophysin) and post-synaptic (PSD-95) proteins. This effect was dependent on TβRI activation because addition of a pharmacological inhibitor of TGF-β, SB-431542, impaired the formation of synapses between granular neurons. Together, these findings suggest that TGF-β1 has a specific key function in the cerebellum through regulation of excitatory synapse formation between granule neurons. PMID:27199658

  7. Efficiently engineered cell sheet using a complex of polyethylenimine–alginate nanocomposites plus bone morphogenetic protein 2 gene to promote new bone formation

    PubMed Central

    Jin, Han; Zhang, Kai; Qiao, Chunyan; Yuan, Anliang; Li, Daowei; Zhao, Liang; Shi, Ce; Xu, Xiaowei; Ni, Shilei; Zheng, Changyu; Liu, Xiaohua; Yang, Bai; Sun, Hongchen

    2014-01-01

    Regeneration of large bone defects is a common clinical problem. Recently, stem cell sheet has been an emerging strategy in bone tissue engineering. To enhance the osteogenic potential of stem cell sheet, we fabricated bone morphogenetic protein 2 (BMP-2) gene-engineered cell sheet using a complex of polyethylenimine–alginate (PEI–al) nanocomposites plus human BMP-2 complementary(c)DNA plasmid, and studied its osteogenesis in vitro and in vivo. PEI–al nanocomposites carrying BMP-2 gene could efficiently transfect bone marrow mesenchymal stem cells. The cell sheet was made by culturing the cells in medium containing vitamin C for 10 days. Assays on the cell culture showed that the genetically engineered cells released the BMP-2 for at least 14 days. The expression of osteogenesis-related gene was increased, which demonstrated that released BMP-2 could effectively induce the cell sheet osteogenic differentiation in vitro. To further test the osteogenic potential of the cell sheet in vivo, enhanced green fluorescent protein or BMP-2-producing cell sheets were treated on the cranial bone defects. The results indicated that the BMP-2-producing cell sheet group was more efficient than other groups in promoting bone formation in the defect area. Our results suggested that PEI–al nanocomposites efficiently deliver the BMP-2 gene to bone marrow mesenchymal stem cells and that BMP-2 gene-engineered cell sheet is an effective way for promoting bone regeneration. PMID:24855355

  8. Beta Cell Formation in vivo Through Cellular Networking, Integration and Processing (CNIP) in Wild Type Adult Mice.

    PubMed

    Doiron, Bruno; Hu, Wenchao; DeFronzo, Ralph A

    2016-01-01

    Insulin replacement therapy is essential in type 1 diabetic individuals and is required in ~40- 50% of type 2 diabetics during their lifetime. Prior attempts at beta cell regeneration have relied upon pancreatic injury to induce beta cell proliferation, dedifferentiation and activation of the embryonic pathway, or stem cell replacement. We report an alternative method to transform adult non-stem (somatic) cells into pancreatic beta cells. The Cellular Networking, Integration and Processing (CNIP) approach targets cellular mechanisms involved in pancreatic function in the organ's adult state and utilizes a synergistic mechanism that integrates three important levels of cellular regulation to induce beta cell formation: (i) glucose metabolism, (ii) membrane receptor function, and (iii) gene transcription. The aim of the present study was to induce pancreatic beta cell formation in vivo in adult animals without stem cells and without dedifferentiating cells to recapitulate the embryonic pathway as previously published (1-3). Our results employing CNIP demonstrate that: (i) insulin secreting cells can be generated in adult pancreatic tissue in vivo and circumvent the problem of generating endocrine (glucagon and somatostatin) cells that exert deleterious effects on glucose homeostasis, and (ii) longterm normalization of glucose tolerance and insulin secretion can be achieved in a wild type diabetic mouse model. The CNIP cocktail has the potential to be used as a preventative or therapeutic treatment or cure for both type 1 and type 2 diabetes. PMID:26696016

  9. Role of the von Hippel-Lindau tumor suppressor gene in the formation of beta1-integrin fibrillar adhesions.

    PubMed

    Esteban-Barragán, Miguel A; Avila, Pilar; Alvarez-Tejado, Miguel; Gutiérrez, M Dolores; García-Pardo, Angeles; Sánchez-Madrid, Francisco; Landázuri, Manuel O

    2002-05-15

    The von Hippel-Lindau tumor suppressor gene (VHL) is absent or inactivated in the VHLcancer syndrome and in most sporadic renal cancers. VHL is requiredfor the assembly of a proper extracellular fibronectin matrix, although the exact mechanism remains unknown. In this report, we demonstrate that 786-O renal cancer cells are unable to organize an adequate matrix even in the presence of an excess of exogenous fibronectin. Because the formation of integrin fibrillar adhesions plays a pivotal role in the organization of extracellular fibronectin, we next examined the expression and subcellular distribution of integrins in VHL- cells and their wild-type VHL stably transfected counterparts. The levels of beta1 and alphav integrins were increased in VHL- cells when compared with VHL+ transfectants. Early after plating, both VHL+ and VHL- cells were capable of assembling classic "patch-like" alphav focal contacts. As the culture advanced and cells became confluent, alphav integrins partly relocated to the intercellular junctions in VHL+ transfectants, which then developed large beta1 fibrillar-type adhesions and anchored firmly to the substrate. In contrast, confluent VHL- cells were unable to assemble beta1 fibrillar adhesions, and alphav focal contacts remained unchanged at all stages of the culture. Exogenous activation of beta1 integrins with either divalent cations or activating antibodies partly restored the capability of VHL- cells to assemble beta1 fibrillar adhesions and fibronectin fibers. Finally, pulse-chase studies of metabolically labeled 786-O cells revealed that the maturation of the common beta1-integrin chain was delayed in VHL- cells when compared with VHL+ cells. Our results show that VHL is an important regulator of integrins and is essential for the formation of beta1 fibrillar adhesions. These findings help to explain the abnormal extracellular matrix organization and increased motility of VHL- renal cancer cells. PMID:12019174

  10. Formation and evolution of flapping and ballooning waves in magnetospheric plasma sheet

    NASA Astrophysics Data System (ADS)

    Ma, J. Z. G.; Hirose, A.

    2016-05-01

    By adopting Lembége & Pellat's 2D plasma-sheet model, we investigate the flankward flapping motion and Sunward ballooning propagation driven by an external source (e.g., magnetic reconnection) produced initially at the sheet center. Within the ideal MHD framework, we adopt the WKB approximation to obtain the Taylor-Goldstein equation of magnetic perturbations. Fourier spectral method and Runge-Kutta method are employed in numerical simulations, respectively, under the flapping and ballooning conditions. Studies expose that the magnetic shears in the sheet are responsible for the flapping waves, while the magnetic curvature and the plasma gradient are responsible for the ballooning waves. In addition, the flapping motion has three phases in its temporal development: fast damping phase, slow recovery phase, and quasi-stabilized phase; it is also characterized by two patterns in space: propagating wave pattern and standing wave pattern. Moreover, the ballooning modes are gradually damped toward the Earth, with a wavelength in a scale size of magnetic curvature or plasma inhomogeneity, only 1-7% of the flapping one; the envelops of the ballooning waves are similar to that of the observed bursty bulk flows moving toward the Earth.

  11. Origin of life. Primordial genetics: Information transfer in a pre-RNA world based on self-replicating beta-sheet amyloid conformers.

    PubMed

    Maury, Carl Peter J

    2015-10-01

    The question of the origin of life on Earth can largely be reduced to the question of what was the first molecular replicator system that was able to replicate and evolve under the presumably very harsh conditions on the early Earth. It is unlikely that a functional RNA could have existed under such conditions and it is generally assumed that some other kind of information system preceded the RNA world. Here, I present an informational molecular system that is stable, self-replicative, environmentally responsive, and evolvable under conditions characterized by high temperatures, ultraviolet and cosmic radiation. This postulated pregenetic system is based on the amyloid fold, a functionally unique polypeptide fold characterized by a cross beta-sheet structure in which the beta strands are arranged perpendicular to the fiber axis. Beside an extraordinary structural robustness, the amyloid fold possesses a unique ability to transmit information by a three-dimensional templating mechanism. In amyloidogenesis short peptide monomers are added one by one to the growing end of the fiber. From the same monomeric subunits several structural variants of amyloid may be formed. Then, in a self-replicative mode, a specific amyloid conformer can act as a template and confer its spatially encoded information to daughter molecular entities in a repetitive way. In this process, the specific conformational information, the spatially changed organization, is transmitted; the coding element is the steric zipper structure, and recognition occurs by amino acid side chain complementarity. The amyloid information system fulfills several basic requirements of a primordial evolvable replicator system: (i) it is stable under the presumed primitive Earth conditions, (ii) the monomeric building blocks of the informational polymer can be formed from available prebiotic compounds, (iii) the system is self-assembling and self-replicative and (iv) it is adaptive to changes in the environment and

  12. The Growth of Magma Bodies by Amalgamation of Discrete Sheet Intrusions: Implications for the Formation of Magma Chambers

    NASA Astrophysics Data System (ADS)

    Annen, C.

    2007-12-01

    Until recently, igneous bodies (plutons and magma chambers) were commonly considered to be approximately spherical bodies, rapidly emplaced into the crust. However, field, structural, geophysical, and geochronological studies indicate that many plutons are low aspect-ratio tabular bodies (sills) that are formed by the amalgamation of successive discrete magma pulses. The thermal evolution of an igneous body that grows by accretion of thin magma sheets is fundamentally different from the evolution of a rapidly emplaced magma sphere or of a single thick magma sill. In thin sheet intrusions, the heat loss is through the walls of the sheets and the temperatures within the intrusions do not depend on the volumes injected but on the one-dimension sheets emplacement rate. The first sheets injected in a cold crust rapidly cool down and solidify. The ability of successive intrusions to stay at high temperature and eventually build up a long-lived magma chamber is controlled by the emplacement rate. Heat transfer modeling applied in the context of a volcanic arc shows that average emplacement rates of at least several centimeters per year and an incubation time of tens thousands of years are needed for a persistent magma chamber to form. During the incubation time, the intrusions solidify and when a chamber of high melt fraction magma eventually grows, the volume of eruptible magma only form a small part of the total intruded volume. The emplacement rate of plutons is controversial. Geochronological data suggest that some plutons may be emplaced over millions years. For a pluton that is assembled at a slow rate of a few millimeters per year, millions of years are needed, over which kilometric thicknesses are intruded, before a volume of magma larger than the size of a single intrusion becomes mobile and eruptible. In many cases, volcanic products may come from a deep source without being associated with a long-lived upper crust magma chamber. If volcanism is associated with

  13. Design study of the geometry of the blanking tool to predict the burr formation of Zircaloy-4 sheet

    NASA Astrophysics Data System (ADS)

    Ha, Jisun; Lee, Hyungyil; Kim, Dongchul; Kim, Naksoo

    2013-12-01

    In this work, we investigated factors that influence burr formation for zircaloy-4 sheet used for spacer grids of nuclear fuel roads. Factors we considered are geometric factors of punch. We changed clearance and velocity in order to consider the failure parameters, and we changed shearing angle and corner radius of L-shaped punch in order to consider geometric factors of punch. First, we carried out blanking test with failure parameter of GTN model using L-shaped punch. The tendency of failure parameters and geometric factors that affect burr formation by analyzing sheared edges is investigated. Consequently, geometric factor's influencing on the burr formation is also high as failure parameters. Then, the sheared edges and burr formation with failure parameters and geometric factors is investigated using FE analysis model. As a result of analyzing sheared edges with the variables, we checked geometric factors more affect burr formation than failure parameters. To check the reliability of the FE model, the blanking force and the sheared edges obtained from experiments are compared with the computations considering heat transfer.

  14. Immunodetection of pectin and arabinogalactan protein epitopes during pollen exine formation of Beta vulgaris L.

    PubMed

    Majewska-Sawka, Anna; Rodriguez-Garcia, Maria Isabel

    2006-08-01

    We present the results of ultrastructural and immunocytochemical studies of sugar beet microsporocytes during the developmental phase that begins with the first meiotic metaphase and ends with the formation of young tetrads. The most prominent feature noted during this period of microsporogenesis was the presence of numerous cisternae of endoplasmic reticulum which frequently lie perpendicular to the surface of the plasma membrane and eventually fuse to it. Microscopic observations have been combined with the detection of several carbohydrate epitopes representing pectins and arabinogalactan proteins in the primexine and incipient exine. Pectin domains that possess both low and highly methylesterified epitopes, as well as pectin side chains enriched in (1-->4)-beta-D-galactose residues, are deposited in this young microspore wall. The epitopes of arabinogalactan protein that bind to JIM13, JIM8, and LM2 antibodies are localised within the callose wall surrounding posttelophase tetrads. The possibility of endoplasmic-reticulum involvement in the synthesis, transport, or metabolism of several microspore wall compounds is discussed.

  15. Formation of sheet plumes, current coils, and helical magnetic fields in a spherical magnetohydrodynamic dynamo

    NASA Astrophysics Data System (ADS)

    Miyagoshi, Takehiro; Kageyama, Akira; Sato, Tetsuya

    2011-07-01

    Aiming at understanding of magnetic field generation process in rapidly rotating stars and planets represented by the Earth, computer simulations of magnetohydrodynamic (MHD) dynamo were performed in a rotating spherical shell geometry. Thermal convection and dynamo process with Ekman number of the order of 10-7 were studied. New structures of convection motion, dynamo-generated electrical current, and magnetic field are found. The flow is organized as a set of thin, sheet-like plumes. The current is made of small-scale coil structure with magnetic flux tubes within each of the coil. These flux tubes are connected each other to form a large scale helical magnetic field structure.

  16. Presence of a glycine-cysteine-rich beta-protein in the oberhautchen layer of snake epidermis marks the formation of the shedding layer.

    PubMed

    Alibardi, Lorenzo

    2014-11-01

    The complex differentiation of snake epidermis largely depends on the variation in the production of glycine-cysteine-rich versus glycine-rich beta-proteins (beta-keratins) that are deposited on a framework of alpha-keratins. The knowledge of the amino acid sequences of beta-proteins in the snake Pantherophis guttatus has allowed the localization of a glycine-cysteine-rich beta-protein in the spinulated oberhautchen layer of the differentiating shedding complex before molting takes place. This protein decreases in the beta-layer and disappears in mesos and alpha-layers. Conversely, while the mRNA for a glycine-rich beta-protein is highly expressed in differentiating beta-cells, the immunolocalization for this protein is low in these cells. This discrepancy between expression and localization suggests that the epitope in glycine-rich beta-proteins is cleaved or modified by posttranslational processes that take place during the differentiation and maturation of the beta-layer. The present study suggests that among the numerous beta-proteins coded in the snake genome to produce epidermal layers with different textures, the glycine-cysteine-rich beta-protein marks the shedding complex formed between alpha- and beta-layers that allows for molting while its disappearance between the beta- and alpha-layers (mesos region for scale growth) is connected to the formation of the alpha-layers.

  17. Constraining the Late Pleistocene history of the Laurentide Ice Sheet by dating the Missinaibi Formation, Hudson Bay Lowlands, Canada

    NASA Astrophysics Data System (ADS)

    Dalton, April S.; Finkelstein, Sarah A.; Barnett, Peter J.; Forman, Steven L.

    2016-08-01

    Well-dated paleorecords from periods prior to the Last Glacial Maximum (LGM) are important for validating models of ice sheet build-up and growth. However, owing to glacial erosion, most Late Pleistocene records lie outside of the previously glaciated region, which limits their ability to inform about the dynamics of paleo-ice sheets. Here, we evaluate new and previously published chronology data from the Missinaibi Formation, a Pleistocene-aged deposit in the Hudson Bay Lowlands (HBL), Canada, located near the geographic center of the Laurentide Ice Sheet (LIS). Available radiocarbon (AMS = 44, conventional = 36), amino acid (n = 13), uranium-thorium (U-Th, n = 14), thermoluminescence (TL, n = 15) and optically stimulated luminescence (OSL, n = 5) data suggest that an ice-free HBL may have been possible during parts of Marine Isotope Stage 7 (MIS 7; ca. 243,000 to ca. 190,000 yr BP), MIS 5 (ca. 130,000 to ca. 71,000 yr BP) and MIS 3 (ca. 29,000 to ca. 57,000). While MIS 7 and MIS 5 are well-documented interglacial periods, the development of peat, forest bed and fluvial deposits dating to MIS 3 (n = 20 radiocarbon dates; 4 TL dates, 3 OSL dates), suggests that the LIS retreated and remained beyond, or somewhere within, the boundaries of the HBL during this interstadial. Ice sheet models approximate the margin of the LIS to Southern Ontario during this time, which is 700 km south of the HBL. Therefore, if correct, our data help constrain a significantly different configuration and dynamicity for the LIS than previously modelled. We can find no chronological basis to discount the MIS 3 age assignments. However, since most data originate from radiocarbon dates lying close to the reliable limit of this geochronometer, future work on dating the Missinaibi Formation using other geochronological methods (e.g. U-Th, OSL) is necessary in order to confirm the age estimates and strengthen the boundaries of the LIS during this period.

  18. Magnetic relaxation, current sheets, and structure formation in an extremely Tenuous fluid medium

    SciTech Connect

    Bajer, K.; Moffatt, H. K.

    2013-12-20

    The process of relaxation of a unidirectional magnetic field in a highly conducting tenuous fluid medium is considered. Null points of the field play a critical role in this process. During an initial stage of relaxation, variations in magnetic pressure are eliminated, and current sheets build up in the immediate neighborhood of null points. This initial phase is followed by a long diffusive phase of slow algebraic decay of the field, during which fluid is continuously sucked into the current sheets, leading to exponential growth of fluid density and concentration of mass around the null points, which show a tendency to cluster. Ultimately, this second phase of algebraic decay gives way to a final period of exponential decay of the field. The peaks of density at the null points survive as a fossil relic of the decay process. Numerical solution of the governing equations provides convincing confirmation of this three-stage scenario. Generalizations to two- and three-dimensional fields are briefly considered.

  19. Conformational stability of fibrillar amyloid-beta oligomers via protofilament pair formation - a systematic computational study.

    PubMed

    Kahler, Anna; Sticht, Heinrich; Horn, Anselm H C

    2013-01-01

    Amyloid-[Formula: see text] (A[Formula: see text]) oligomers play a crucial role in Alzheimer's disease due to their neurotoxic aggregation properties. Fibrillar A[Formula: see text] oligomerization can lead to protofilaments and protofilament pairs via oligomer elongation and oligomer association, respectively. Small fibrillar oligomers adopt the protofilament topology, whereas fibrils contain at least protofilament pairs. To date, the underlying growth mechanism from oligomers to the mature fibril still remains to be elucidated. Here, we performed all-atom molecular dynamics simulations in explicit solvent on single layer-like protofilaments and fibril-like protofilament pairs of different size ranging from the tetramer to the 48-mer. We found that the initial U-shaped topology per monomer is maintained over time in all oligomers. The observed deviations of protofilaments from the starting structure increase significantly with size due to the twisting of the in-register parallel [Formula: see text]-sheets. This twist causes long protofilaments to be unstable and leads to a breakage. Protofilament pairs, which are stabilized by a hydrophobic interface, exhibit more fibril-like properties such as the overall structure and the twist angle. Thus, they can act as stable conformational templates for further fibril growth. Key properties like the twist angle, shape complementarity, and energetics show a size-dependent behavior so that small oligomers favor the protofilament topology, whereas large oligomers favor the protofilament pair topology. The region for this conformational transition is at the size of approximately twelve A[Formula: see text] monomers. From that, we propose the following growth mechanism from A[Formula: see text] oligomers to fibrils: (1) elongation of short protofilaments; (2) breakage of large protofilaments; (3) formation of short protofilament pairs; and (4) elongation of protofilament pairs.

  20. Morphological properties of tunnel valleys of the southern sector of the Laurentide Ice Sheet and implications for their formation

    NASA Astrophysics Data System (ADS)

    Livingstone, Stephen J.; Clark, Chris D.

    2016-07-01

    Tunnel valleys have been widely reported on the bed of former ice sheets and are considered an important expression of subglacial meltwater drainage. Although known to have been cut by erosive meltwater flow, the water source and development of channels has been widely debated; ranging between outburst flood events through to gradually occurring channel propagation. We have mapped and analysed the spatial pattern and morphometry of tunnel valleys and associated glacial landforms along the southern sector of the former Laurentide Ice Sheet from high-resolution digital elevation models. Around 2000 tunnel valleys have been mapped, revealing an organised pattern of sub-parallel, semi-regularly spaced valleys that form in distinctive clusters. The tunnel valleys are typically < 20 km long, and 0.5-3 km wide, although their width varies considerably down-valley. They preferentially terminate at moraines, which suggests that formation is time dependent; while we also observe some tunnel valleys that have grown headwards out of hill-hole pairs. Analysis of cross-cutting relationships between tunnel valleys, moraines and outwash fans permits reconstruction of channel development in relation to the retreating ice margin. This palaeo-drainage reconstruction demonstrates incremental growth of most valleys, with some used repeatedly or for long periods, during deglaciation, while others were abandoned shortly after their formation. Our data and interpretation support gradual (rather than a single-event) formation of most tunnel valleys with secondary contributions from flood drainage of subglacial and or supraglacially stored water down individual tunnel valleys. The distribution and morphology of tunnel valleys is shown to be sensitive to regional factors such as basal thermal regime, ice and bed topography, timing and climate.

  1. Formation of adherens and communicating junctions coordinate the differentiation of the shedding-layer and beta-epidermal generation in regenerating lizard epidermis.

    PubMed

    Alibardi, Lorenzo

    2014-06-01

    In the lizard epidermis, the formation of a stratified alpha- and beta-layer, separated by a shedding complex for molting, suggests that keratinocytes communicate in a coordinated manner after they leave the basal layers during the shedding cycle. I have therefore studied the localization of cell junctional proteins such as beta-catenin and connexins 43 and 26 during scale regeneration in lizard using immunocytochemistry. Beta-catenin is also detected in nuclei of basal cells destined to give rise to the Oberhäutchen and beta-cells suggesting activation of the Wnt-pathway during beta-cell differentiation. The observations show that cells of the entire shedding layer (clear and Oberhäutchen) and beta-layer are connected by beta-catenin (adherens junctions) and connexins (communicating junctions) during their differentiation. This likely cell coupling determines the formation of a distinct shedding and beta-layer within the regenerating epidermis. The observed pattern of cell junctional stratification suggests that after departing from the basal layer Oberhäutchen and beta-cells form a continuous communicating compartment that coordinates the contemporaneous differentiation along the entire scale. While the beta-layer matures the junctions are lost while other cell junctions are formed in the following mesos- and alpha-cell layers. This process determines the formation of layers with different texture (harder or softer) and the precise localization of the shedding layer within lizard epidermis.

  2. Estradiol acts via estrogen receptors alpha and beta on pathways important for synaptic plasticity in the mouse hippocampal formation

    PubMed Central

    Spencer-Segal, Joanna L.; Tsuda, Mumeko C.; Mattei, Larissa; Waters, Elizabeth M.; Romeo, Russell D.; Milner, Teresa A.; McEwen, Bruce S.; Ogawa, Sonoko

    2012-01-01

    Estradiol affects hippocampal-dependent spatial memory and underlying structural and electrical synaptic plasticity in female mice and rats. Using estrogen receptor (ER) alpha and beta knockout mice and wild-type littermates, we investigated the role of ERs in estradiol effects on multiple pathways important for hippocampal plasticity and learning. Six hours of estradiol administration increased immunoreactivity for phosphorylated Akt throughout the hippocampal formation, while 48 hours of estradiol increased immunoreactivity for phosphorylated TrkB receptor. Estradiol effects on phosphorylated Akt and TrkB immunoreactivities were abolished in ER alpha and ER beta knockout mice. Estradiol also had distinct effects on immunoreactivity for PSD-95 and BDNF mRNA in ER alpha and beta knockout mice. Thus, estradiol acts through both ERs alpha and beta in several subregions of the hippocampal formation. The different effects of estradiol at 6 and 48 hours indicate that several mechanisms of estrogen receptor signaling contribute to this female hormone’s influence on hippocampal synaptic plasticity. By further delineating these mechanisms, we will better understand and predict the effects of endogenous and exogenous ovarian steroids on mood, cognition, and other hippocampal-dependent behaviors. PMID:22133892

  3. Beta4 integrin-dependent formation of polarized three-dimensionalarchitecture confers resistance to apoptosis in normal and malignantmammary epithelium

    SciTech Connect

    Weaver, Valerie M.; Lelievre, Sophie; Lakins, Johnathon N.; Chrenek, Micah A.; Jones, Jonathan C.R.; Giancotti, Filippo; Werb, Zena; Bissell, Mina J.

    2002-08-27

    Tumor cells can evade chemotherapy by acquiring resistanceto apoptosis. We investigated the molecular mechanism whereby malignantand nonmalignant mammary epithelial cells become insensitive toapoptosis. We show that regardless of growth status formation ofpolarized, three-dimensional structures driven by basement membraneconfers protection to apoptosis in both nonmalignant and malignantmammary epithelial cells. By contrast, irrespective of their malignantstatus, nonpolarized structures are sensitive to induction of apoptosis.Resistance to apoptosis requires ligation of beta4 integrins, whichregulates tissue polarity, hemidesmosome formation and NFkB activation.Expression of beta4 integrin that lacks the hemidesmosome targetingdomain interferes with tissue polarity and NFkB activation and permitsapoptosis. These results indicate that integrin-induced polarity maydrive tumor cell resistance to apoptosis-inducing agents via effects onNFkB.

  4. From Boron Cluster to Two-Dimensional Boron Sheet on Cu(111) Surface: Growth Mechanism and Hole Formation

    PubMed Central

    Liu, Hongsheng; Gao, Junfeng; Zhao, Jijun

    2013-01-01

    As attractive analogue of graphene, boron monolayers have been theoretically predicted. However, due to electron deficiency of boron atom, synthesizing boron monolayer is very challenging in experiments. Using first-principles calculations, we explore stability and growth mechanism of various boron sheets on Cu(111) substrate. The monotonic decrease of formation energy of boron cluster BN with increasing cluster size and low diffusion barrier for a single B atom on Cu(111) surface ensure continuous growth of two-dimensional (2D) boron cluster. During growth process, hexagonal holes can easily arise at the edge of a 2D triangular boron cluster and then diffuse entad. Hence, large-scale boron monolayer with mixed hexagonal-triangular geometry can be obtained via either depositing boron atoms directly on Cu(111) surface or soft landing of small planar BN clusters. Our theoretical predictions would stimulate further experiments of synthesizing boron sheets on metal substrates and thus enrich the variety of 2D monolayer materials. PMID:24241341

  5. Formation and stability of {beta}-quartz solid-solution phase in the Li-Si-Al-O-N system

    SciTech Connect

    Nordmann, A.; Cheng, Y.B.

    1997-12-01

    The development of crystalline phases in lithium oxynitride glass-ceramics was examined, with particular emphasis placed on the effect of the nitrogen source (AlN or Si{sub 3}N{sub 4}) on the formation and stability of a {beta}-quartz solid-solution (ss) phase. Oxynitride glasses derived from the Li-Si-Al-O-N system were heated-treated at temperatures up to 1,200 C to yield glass-ceramics in which {beta}-quartz(ss) and {beta}-spodumene(ss) of approximate composition Li{sub 2}O {center_dot} Al{sub 2}O{sub 3} {center_dot} 4SiO{sub 2} formed as major phases and in which X-phase (Si{sub 3}Al{sub 6}O{sub 12}N{sub 2}) and silicon oxynitride (Si{sub 2}N{sub 2}O) were present as minor phases. The nitrogen-containing {beta}-quartz(ss) phase that was prepared with AlN was stable at 1,200 C; however, the use of Si{sub 3}N{sub 4} as the nitrogen source was significantly less effective in promoting such thermal stabilization. Lattice parameter measurements revealed that AlN and Si{sub 3}N{sub 4} had different effects on the crystalline structures, and it was proposed that the enhanced thermal stability of the {beta}-quartz(ss) phase that was prepared with AlN was due to both the replacement of oxygen by nitrogen and the positioning of excess Al{sup 3+} ions into interstitial sites within the {beta}-quartz(ss) crystal lattice.

  6. Formation of ferromagnetic interface between {beta}-FeSi{sub 2} and Si(111) substrate

    SciTech Connect

    Hattori, Azusa N.; Hattori, Ken; Kodama, Kenji; Hosoito, Nobuyoshi; Daimon, Hiroshi

    2007-11-12

    Epitaxial {beta}-FeSi{sub 2} thin films were grown on Si(111)7x7 clean surfaces by solid phase epitaxy in ultrahigh vacuum: iron deposition at low temperature and subsequent annealing. We found that a ferromagnetic interface layer of iron-rich silicides forms between a {beta}-FeSi{sub 2} surface layer and a Si(111) substrate spontaneously from transmission electron microscopy observations and magnetization measurements.

  7. Molecular cloning of pigeon UDP-galactose:beta-D-galactoside alpha1,4-galactosyltransferase and UDP-galactose:beta-D-galactoside beta1,4-galactosyltransferase, two novel enzymes catalyzing the formation of Gal alpha1-4Gal beta1-4Gal beta1-4GlcNAc sequence.

    PubMed

    Suzuki, Noriko; Yamamoto, Kazuo

    2010-02-19

    We previously found that pigeon IgG possesses unique N-glycan structures that contain the Gal alpha1-4Gal beta1-4Gal beta1-4GlcNAc sequence at their nonreducing termini. This sequence is most likely produced by putative alpha1,4- and beta1,4-galactosyltransferases (GalTs), which are responsible for the biosynthesis of the Gal alpha1-4Gal and Gal beta1-4Gal sequences on the N-glycans, respectively. Because no such glycan structures have been found in mammalian glycoproteins, the biosynthetic enzymes that produce these glycans are likely to have distinct substrate specificities from the known mammalian GalTs. To study these enzymes, we cloned the pigeon liver cDNAs encoding alpha4GalT and beta4GalT by expression cloning and characterized these enzymes using the recombinant proteins. The deduced amino acid sequence of pigeon alpha4GalT has 58.2% identity to human alpha4GalT and 68.0 and 66.6% identity to putative alpha4GalTs from chicken and zebra finch, respectively. Unlike human and putative chicken alpha4GalTs, which possess globotriosylceramide synthase activity, pigeon alpha4GalT preferred to catalyze formation of the Gal alpha1-4Gal sequence on glycoproteins. In contrast, the sequence of pigeon beta4GalT revealed a type II transmembrane protein consisting of 438 amino acid residues, with no significant homology to the glycosyltransferases so far identified from mammals and chicken. However, hypothetical proteins from zebra finch (78.8% identity), frogs (58.9-60.4%), zebrafish (37.1-43.0%), and spotted green pufferfish (43.3%) were similar to pigeon beta4GalT, suggesting that the pigeon beta4GalT gene was inherited from the common ancestors of these vertebrates. The sequence analysis revealed that pigeon beta4GalT and its homologs form a new family of glycosyltransferases.

  8. Beta sheet 2-alpha helix C loop of cytochrome P450 reductase serves as a docking site for redox partners.

    PubMed

    Jang, Hyun-Hee; Jamakhandi, Arvind P; Sullivan, Shane Z; Yun, Chul-Ho; Hollenberg, Paul F; Miller, Grover P

    2010-06-01

    As a promiscuous redox partner, the biological role of cytochrome P450 reductase (CPR) depends significantly on protein-protein interactions. We tested a hypothesized CPR docking site by mutating D113, E115, and E116 to alanine and assaying activity toward various electron acceptors as a function of ionic strength. Steady-state cytochrome c studies demonstrated the mutations improved catalytic efficiency and decreased the impact of ionic strength on catalytic parameters when compared to wild type. Based on activity toward 7-ethoxy-4-trifluoro-methylcoumarin, CYP2B1 and CPR favored formation of an active CYP2B1*CPR complex and inactive (CYP2B1)(2)*CPR complex until higher ionic strength whereby only the binary complex was observed. The mutations increased dissociation constants only for the binary complex and suppressed the ionic strength effect. Studies with a non-binding substrate, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) suggest changes in activity toward cytochrome c and CYP2B1 reflect alterations in the route of electron transfer caused by the mutations. Electrostatic modeling of catalytic and binding parameters confirmed the importance of D113 and especially the double mutant E115 and E116 as mediators in forming charge-charge interactions between CPR and complex partners. PMID:20152939

  9. On the formation of the tunnel valleys of the southern Laurentide ice sheet

    USGS Publications Warehouse

    Hooke, R. LeB; Jennings, C.E.

    2006-01-01

    Catastrophic releases of meltwater, produced by basal melting and stored for decades in subglacial reservoirs at high pressure, may have been responsible for eroding the broad, deep tunnel valleys that are common along the margins of some lobes of the southern Laurentide ice sheet. We surmise that these releases began when the high water pressure was transmitted to the margin through the substrate. The water pressure in the substrate at the margin would then have been significantly above the overburden pressure, leading to sapping failure. Headward erosion of a conduit in the substrate (piping) could then tap the stored water, resulting in the outburst. In some situations, development of a siphon may have lowered the reservoir below its overflow level, thus tapping additional water. Following the flood, the seal could have reformed and the reservoir refilled, setting up conditions for another outburst. Order of magnitude calculations suggest that once emptied, a subglacial reservoir could refill in a matter of decades. The amount of water released during several outbursts appears to be sufficient to erode a tunnel valley. We think that tunnel valleys are most likely to have formed in this way where and when the glacier margin was frozen to the bed and permafrost extended from the glacier forefield several kilometers back under the glacier, as reservoirs would then have been larger and more common, and the seal more robust and more likely to reform after an outburst. ?? 2006 Elsevier Ltd. All rights reserved.

  10. Reduction of Liquid Clad Formation Due to Solid State Diffusion in Clad Brazing Sheet

    NASA Astrophysics Data System (ADS)

    Benoit, Michael J.; Whitney, Mark A.; Wells, Mary A.; Winkler, Sooky

    2016-09-01

    Warm forming operations have shown promise in expanding automotive heat exchanger designs by increasing forming limits of clad brazing sheet. The impact of isothermal holds below the clad melting temperature on subsequent brazeability has not previously been studied in detail. The effect of these holds on brazeability, as measured by the clad thickness loss due to solid state diffusion of Si out of the clad layer prior to clad melting, was assessed through parallel DSC and optical microscopy measurements, as well as through the use of a previously developed model. EPMA measurements were also performed to support the other measures. Overall, the same trends were predicted by DSC, microscopy, and the theoretical model; however, the DSC predictions were unable to accurately predict remaining clad thickness prior to melting, even after correcting the data for clad-core interactions. Microscopy measurements showed very good agreement with the model predictions, although there were slight discrepancies at short hold times due to the inability of the model to account for clad loss during heating to the brazing temperature. Further microscopy measurements showed that when the heating rate is set below a critical value, there is a reduction in the clad thickness from the as-received condition.

  11. β-sheet-like formation during the mechanical unfolding of prion protein

    SciTech Connect

    Tao, Weiwei; Cao, Penghui; Park, Harold S.; Yoon, Gwonchan; Eom, Kilho

    2015-09-28

    Single molecule experiments and simulations have been widely used to characterize the unfolding and folding pathways of different proteins. However, with few exceptions, these tools have not been applied to study prion protein, PrP{sup C}, whose misfolded form PrP{sup Sc} can induce a group of fatal neurodegenerative diseases. Here, we apply novel atomistic modeling based on potential energy surface exploration to study the constant force unfolding of human PrP at time scales inaccessible with standard molecular dynamics. We demonstrate for forces around 100 pN, prion forms a stable, three-stranded β-sheet-like intermediate configuration containing residues 155-214 with a lifetime exceeding hundreds of nanoseconds. A mutant without the disulfide bridge shows lower stability during the unfolding process but still forms the three-stranded structure. The simulations thus not only show the atomistic details of the mechanically induced structural conversion from the native α-helical structure to the β-rich-like form but also lend support to the structural theory that there is a core of the recombinant PrP amyloid, a misfolded form reported to induce transmissible disease, mapping to C-terminal residues ≈160-220.

  12. On the formation of the tunnel valleys of the southern Laurentide ice sheet

    NASA Astrophysics Data System (ADS)

    Hooke, Roger LeB.; Jennings, Carrie E.

    2006-06-01

    Catastrophic releases of meltwater, produced by basal melting and stored for decades in subglacial reservoirs at high pressure, may have been responsible for eroding the broad, deep tunnel valleys that are common along the margins of some lobes of the southern Laurentide ice sheet. We surmise that these releases began when the high water pressure was transmitted to the margin through the substrate. The water pressure in the substrate at the margin would then have been significantly above the overburden pressure, leading to sapping failure. Headward erosion of a conduit in the substrate (piping) could then tap the stored water, resulting in the outburst. In some situations, development of a siphon may have lowered the reservoir below its overflow level, thus tapping additional water. Following the flood, the seal could have reformed and the reservoir refilled, setting up conditions for another outburst. Order of magnitude calculations suggest that once emptied, a subglacial reservoir could refill in a matter of decades. The amount of water released during several outbursts appears to be sufficient to erode a tunnel valley. We think that tunnel valleys are most likely to have formed in this way where and when the glacier margin was frozen to the bed and permafrost extended from the glacier forefield several kilometers back under the glacier, as reservoirs would then have been larger and more common, and the seal more robust and more likely to reform after an outburst.

  13. β-sheet-like formation during the mechanical unfolding of prion protein.

    PubMed

    Tao, Weiwei; Yoon, Gwonchan; Cao, Penghui; Eom, Kilho; Park, Harold S

    2015-09-28

    Single molecule experiments and simulations have been widely used to characterize the unfolding and folding pathways of different proteins. However, with few exceptions, these tools have not been applied to study prion protein, PrP(C), whose misfolded form PrP(Sc) can induce a group of fatal neurodegenerative diseases. Here, we apply novel atomistic modeling based on potential energy surface exploration to study the constant force unfolding of human PrP at time scales inaccessible with standard molecular dynamics. We demonstrate for forces around 100 pN, prion forms a stable, three-stranded β-sheet-like intermediate configuration containing residues 155-214 with a lifetime exceeding hundreds of nanoseconds. A mutant without the disulfide bridge shows lower stability during the unfolding process but still forms the three-stranded structure. The simulations thus not only show the atomistic details of the mechanically induced structural conversion from the native α-helical structure to the β-rich-like form but also lend support to the structural theory that there is a core of the recombinant PrP amyloid, a misfolded form reported to induce transmissible disease, mapping to C-terminal residues ≈160-220. PMID:26429042

  14. β-sheet-like formation during the mechanical unfolding of prion protein

    NASA Astrophysics Data System (ADS)

    Tao, Weiwei; Yoon, Gwonchan; Cao, Penghui; Eom, Kilho; Park, Harold S.

    2015-09-01

    Single molecule experiments and simulations have been widely used to characterize the unfolding and folding pathways of different proteins. However, with few exceptions, these tools have not been applied to study prion protein, PrPC, whose misfolded form PrPSc can induce a group of fatal neurodegenerative diseases. Here, we apply novel atomistic modeling based on potential energy surface exploration to study the constant force unfolding of human PrP at time scales inaccessible with standard molecular dynamics. We demonstrate for forces around 100 pN, prion forms a stable, three-stranded β-sheet-like intermediate configuration containing residues 155-214 with a lifetime exceeding hundreds of nanoseconds. A mutant without the disulfide bridge shows lower stability during the unfolding process but still forms the three-stranded structure. The simulations thus not only show the atomistic details of the mechanically induced structural conversion from the native α-helical structure to the β-rich-like form but also lend support to the structural theory that there is a core of the recombinant PrP amyloid, a misfolded form reported to induce transmissible disease, mapping to C-terminal residues ≈160-220.

  15. Formation of carbon nanoscrolls from graphene sheet: A molecular dynamics study

    NASA Astrophysics Data System (ADS)

    Zhang, Danhui; Yang, Houbo

    2016-12-01

    In recent year, carbon nanoscrolls have attracted intensive attention both in theory and experiments for their unique and excellent fundamental properties and the wide range of potential applications. In this paper, the fabrication of carbon nanoscrolls using graphene and carbon nanotubes has been studied by molecular dynamics (MD) method. The formation mechanism of carbon nanoscrolls has been presented convincing explanations. Furthermore, the position and number of carbon nanotubes also influence the formation of carbon nanoscrolls. Our theoretical results will provide researchers a powerful guide and helpful assistance in designing better targeted programs in experiments.

  16. Formation of nNOS/PSD-95 PDZ dimer requires a preformed beta-finger structure from the nNOS PDZ domain.

    PubMed

    Tochio, H; Mok, Y K; Zhang, Q; Kan, H M; Bredt, D S; Zhang, M

    2000-10-27

    PDZ domains are modular protein units that play important roles in organizing signal transduction complexes. PDZ domains mediate interactions with both C-terminal peptide ligands and other PDZ domains. Here, we used PDZ domains from neuronal nitric oxide synthase (nNOS) and postsynaptic density protein-95 (PSD-95) to explore the mechanism for PDZ-dimer formation. The nNOS PDZ domain terminates with a approximately 30 residue amino acid beta-finger peptide that is shown to be required for nNOS/PSD-95 PDZ dimer formation. In addition, formation of the PDZ dimer requires this beta-finger peptide to be physically anchored to the main body of the canonical nNOS PDZ domain. A buried salt bridge between the beta-finger and the PDZ domain induces and stabilizes the beta-hairpin structure of the nNOS PDZ domain. In apo-nNOS, the beta-finger peptide is partially flexible and adopts a transient beta-strand like structure that is stabilized upon PDZ dimer formation. The flexibility of the NOS PDZ beta-finger is likely to play a critical role in supporting the formation of nNOS/PSD-95 complex. The experimental data also suggest that nNOS PDZ and the second PDZ domain of PSD-95 form a "head-to-tail" dimer similar to the nNOS/syntrophin complex characterized by X-ray crystallography.

  17. Optimal Scaling in Solids Undergoing Ductile Fracture by Void Sheet Formation

    NASA Astrophysics Data System (ADS)

    Fokoua, Landry; Conti, Sergio; Ortiz, Michael

    2014-04-01

    This work is concerned with the derivation of optimal scaling laws, in the sense of matching lower and upper bounds on the energy, for a solid undergoing ductile fracture. The specific problem considered concerns a material sample in the form of an infinite slab of finite thickness subjected to prescribed opening displacements on its two surfaces. The solid is assumed to obey deformation-theory of plasticity and, in order to further simplify the analysis, we assume isotropic rigid-plastic deformations with zero plastic spin. When hardening exponents are given values consistent with observation, the energy is found to exhibit sublinear growth. We regularize the energy through the addition of nonlocal energy terms of the strain-gradient plasticity type. This nonlocal regularization has the effect of introducing an intrinsic length scale into the energy. Under these assumptions, ductile fracture emerges as the net result of two competing effects: whereas the sublinear growth of the local energy promotes localization of deformation to failure planes, the nonlocal regularization stabilizes this process, thus resulting in an orderly progression towards failure and a well-defined specific fracture energy. The optimal scaling laws derived here show that ductile fracture results from localization of deformations to void sheets, and that it requires a well-defined energy per unit fracture area. In particular, fractal modes of fracture are ruled out under the assumptions of the analysis. The optimal scaling laws additionally show that ductile fracture is cohesive in nature, that is, it obeys a well-defined relation between tractions and opening displacements. Finally, the scaling laws supply a link between micromechanical properties and macroscopic fracture properties. In particular, they reveal the relative roles that surface energy and microplasticity play as contributors to the specific fracture energy of the material.

  18. Crystal formation and growth during the hydrothermal synthesis of beta-Ni(OH)2 in one-dimensional nano space.

    PubMed

    Orikasa, Hironori; Karoji, Jyunpei; Matsui, Keitaro; Kyotani, Takashi

    2007-09-14

    Hydrothermal synthesis of beta-Ni(OH)(2) was performed inside uniform carbon-coated nanochannels of an anodic aluminium oxide film. The time course of crystal formation and growth of Ni(OH)(2) in such one-dimensional nano space was observed using transmission electron microscopy (TEM), and the changes in the number and size of crystals with the hydrothermal reaction period were quantitatively analyzed using the TEM images. Moreover, the effect of the channel size (25, 100 and 300 nm in diameter) on the crystal growth was examined. In the early stage of the reaction, the crystal formation and growth of beta-Ni(OH)(2) in the one-dimensional channels took place in the same manner as in conventional hydrothermal synthesis. However, except for the 300 nm-channels, further crystal growth was hampered by the spatial restriction, and it allowed only the growth toward the channel axis. In the case of the 25 nm-channels, many Ni(OH)(2) crystals of less than 40 nm formed initially, but slowly disappeared except for a few that grew larger at the expense of the small crystals. This finding clearly indicates that the crystal growth of Ni(OH)(2) during the whole hydrothermal process was governed by the Ostwald ripening. With this mechanism and the spatial restriction, single crystals of beta-Ni(OH)(2) nanorods with a length of over 150 nm were finally formed.

  19. Mutagenesis and chemical rescue indicate residues involved in beta-aspartyl-AMP formation by Escherichia coli asparagine synthetase B.

    PubMed

    Boehlein, S K; Walworth, E S; Richards, N G; Schuster, S M

    1997-05-01

    Site-directed mutagenesis and kinetic studies have been employed to identify amino acid residues involved in aspartate binding and transition state stabilization during the formation of beta-aspartyl-AMP in the reaction mechanism of Escherichia coli asparagine synthetase B (AS-B). Three conserved amino acids in the segment defined by residues 317-330 appear particularly crucial for enzymatic activity. For example, when Arg-325 is replaced by alanine or lysine, the resulting mutant enzymes possess no detectable asparagine synthetase activity. The catalytic activity of the R325A AS-B mutant can, however, be restored to about 1/6 of that of wild-type AS-B by the addition of guanidinium HCl (GdmHCl). Detailed kinetic analysis of the rescued activity suggests that Arg-325 is involved in stabilization of a pentacovalent intermediate leading to the formation beta-aspartyl-AMP. This rescue experiment is the second example in which the function of a critical arginine residue that has been substituted by mutagenesis is restored by GdmHCl. Mutation of Thr-322 and Thr-323 also produces enzymes with altered kinetic properties, suggesting that these threonines are involved in aspartate binding and/or stabilization of intermediates en route to beta-aspartyl-AMP. These experiments are the first to identify residues outside of the N-terminal glutamine amide transfer domain that have any functional role in asparagine synthesis.

  20. The geologic mapping of Venus using C-1 format: Sheets 75N254, 60N263

    NASA Technical Reports Server (NTRS)

    Shalimov, I. V.

    1992-01-01

    The results of geologic mapping of Venus, produced on the base of Magellan images, are presented. We submit two C-1 format geologic maps with the appropriate legend. The mapping territory was taken from Venera 15 and 16 missions and geologic maps were composed. Magellan images allow us to divide some types of the plains units to determine the lava flow direction and to map with better accuracy.

  1. Unfolding Simulations of Holomyoglobin from Four Mammals: Identification of Intermediates and β-Sheet Formation from Partially Unfolded States

    PubMed Central

    Dasmeh, Pouria; Kepp, Kasper P.

    2013-01-01

    Myoglobin (Mb) is a centrally important, widely studied mammalian protein. While much work has investigated multi-step unfolding of apoMb using acid or denaturant, holomyoglobin unfolding is poorly understood despite its biological relevance. We present here the first systematic unfolding simulations of holoMb and the first comparative study of unfolding of protein orthologs from different species (sperm whale, pig, horse, and harbor seal). We also provide new interpretations of experimental mean molecular ellipticities of myoglobin intermediates, notably correcting for random coil and number of helices in intermediates. The simulated holoproteins at 310 K displayed structures and dynamics in agreement with crystal structures (Rg ∼1.48–1.51 nm, helicity ∼75%). At 400 K, heme was not lost, but some helix loss was observed in pig and horse, suggesting that these helices are less stable in terrestrial species. At 500 K, heme was lost within 1.0–3.7 ns. All four proteins displayed exponentially decaying helix structure within 20 ns. The C- and F-helices were lost quickly in all cases. Heme delayed helix loss, and sperm whale myoglobin exhibited highest retention of heme and D/E helices. Persistence of conformation (RMSD), secondary structure, and ellipticity between 2–11 ns was interpreted as intermediates of holoMb unfolding in all four species. The intermediates resemble those of apoMb notably in A and H helices, but differ substantially in the D-, E- and F-helices, which interact with heme. The identified mechanisms cast light on the role of metal/cofactor in poorly understood holoMb unfolding. We also observed β-sheet formation of several myoglobins at 500 K as seen experimentally, occurring after disruption of helices to a partially unfolded, globally disordered state; heme reduced this tendency and sperm-whale did not display any sheet propensity during the simulations. PMID:24386077

  2. Unfolding simulations of holomyoglobin from four mammals: identification of intermediates and β-sheet formation from partially unfolded states.

    PubMed

    Dasmeh, Pouria; Kepp, Kasper P

    2013-01-01

    Myoglobin (Mb) is a centrally important, widely studied mammalian protein. While much work has investigated multi-step unfolding of apoMb using acid or denaturant, holomyoglobin unfolding is poorly understood despite its biological relevance. We present here the first systematic unfolding simulations of holoMb and the first comparative study of unfolding of protein orthologs from different species (sperm whale, pig, horse, and harbor seal). We also provide new interpretations of experimental mean molecular ellipticities of myoglobin intermediates, notably correcting for random coil and number of helices in intermediates. The simulated holoproteins at 310 K displayed structures and dynamics in agreement with crystal structures (R g ~1.48-1.51 nm, helicity ~75%). At 400 K, heme was not lost, but some helix loss was observed in pig and horse, suggesting that these helices are less stable in terrestrial species. At 500 K, heme was lost within 1.0-3.7 ns. All four proteins displayed exponentially decaying helix structure within 20 ns. The C- and F-helices were lost quickly in all cases. Heme delayed helix loss, and sperm whale myoglobin exhibited highest retention of heme and D/E helices. Persistence of conformation (RMSD), secondary structure, and ellipticity between 2-11 ns was interpreted as intermediates of holoMb unfolding in all four species. The intermediates resemble those of apoMb notably in A and H helices, but differ substantially in the D-, E- and F-helices, which interact with heme. The identified mechanisms cast light on the role of metal/cofactor in poorly understood holoMb unfolding. We also observed β-sheet formation of several myoglobins at 500 K as seen experimentally, occurring after disruption of helices to a partially unfolded, globally disordered state; heme reduced this tendency and sperm-whale did not display any sheet propensity during the simulations. PMID:24386077

  3. Inhibition of amyloid fibril formation of human amylin by N-alkylated amino acid and alpha-hydroxy acid residue containing peptides.

    PubMed

    Rijkers, Dirk T S; Höppener, Jo W M; Posthuma, George; Lips, Cornelis J M; Liskamp, Rob M J

    2002-09-16

    Amyloid deposits are formed as a result of uncontrolled aggregation of (poly)peptides or proteins. Today several diseases are known, for example Alzheimer's disease, Creutzfeldt-Jakob disease, mad cow disease, in which amyloid formation is involved. Amyloid fibrils are large aggregates of beta-pleated sheets and here a general method is described to introduce molecular mutations in order to achieve disruption of beta-sheet formation. Eight backbone-modified amylin derivatives, an amyloidogenic peptide involved in maturity onset diabetes, were synthesized. Their beta-sheet forming properties were studied by IR spectroscopy and electron microscopy. Modification of a crucial amide NH by an alkyl chain led to a complete loss of the beta-sheet forming capacity of amylin. The resulting molecular mutated amylin derivative could be used to break the beta-sheet thus retarding beta-sheet formation of unmodified amylin. Moreover, it was found that the replacement of this amide bond by an ester moiety suppressed fibrillogenesis significantly. Introduction of N-alkylated amino acids and/or ester functionalities-leading to depsipeptides-into amyloidogenic peptides opens new avenues towards novel peptidic beta-sheet breakers for inhibition of beta-amyloid aggregation. PMID:12298020

  4. Carbon nanotube inhibits the formation of β-sheet-rich oligomers of the Alzheimer's amyloid-β(16-22) peptide.

    PubMed

    Li, Huiyu; Luo, Yin; Derreumaux, Philippe; Wei, Guanghong

    2011-11-01

    Alzheimer's disease is associated with the abnormal self-assembly of the amyloid-β (Aβ) peptide into toxic β-rich aggregates. Experimental studies have shown that hydrophobic nanoparticles retard Aβ fibrillation by slowing down the nucleation process; however, the effects of nanoparticles on Aβ oligomeric structures remain elusive. In this study, we investigate the conformations of Aβ(16-22) octamers in the absence and presence of a single-walled carbon nanotube (SWCNT) by performing extensive all-atom replica exchange molecular-dynamics simulations in explicit solvent. Our simulations starting from eight random chains demonstrate that the addition of SWCNT into Aβ(16-22) solution prevents β-sheet formation. Simulation starting from a prefibrillar β-sheet octamer shows that SWCNT destabilizes the β-sheet structure. A detailed analysis of the Aβ(16-22)/SWCNT/water interactions reveals that both the inhibition of β-sheet formation and the destabilization of prefibrillar β-sheets by SWCNT result from the same physical forces: hydrophobic and π-stacking interactions (with the latter playing a more important role). By analyzing the stacking patterns between the Phe aromatic rings and the SWCNT carbon rings, we find that short ring-centroid distances mostly favor parallel orientation, whereas large distances allow all other orientations to be populated. Overall, our computational study provides evidence that SWCNT is likely to inhibit Aβ(16-22) and full-length Aβ fibrillation.

  5. Non-linear Tearing and Flux rope Formation in 3D Null Current Sheets

    NASA Astrophysics Data System (ADS)

    Wyper, P. F.; Pontin, D. I.

    2014-12-01

    The manner in which small scale structure affects the large scale reconnection process in realistic 3D geometries is still an unsolved problem. With the increase in computational resources and improvements in satellite instrumentation, signatures of flux ropes or "plasmoids" are now observed with increasing regularity, yet their formation and dynamics are poorly understood. It has been demonstrated that even at MHD scales, in 2D rapid non-linear tearing of Sweet-Parker-like layers forms multiple magnetic islands ("plasmoids") and allows the reconnection rate to become almost independent of the Lundquist number (the "plasmoid instability"). This work presents some of our recent theoretical work focussing on an analogous instability in a fully 3D geometry. Using results from a series of 3D high resolution MHD simulations, the formation and evolution of fully three dimensional "flux rope" structures following the 3D plasmoid instability will be presented, and their effects on the manner of the reconnection process as a whole discussed.

  6. Effects of the Formation of Al x Cu y Gradient Interfaces on Mechanical Property of Steel/Al Laminated Sheets by Introducing Cu Binding-Sheets

    NASA Astrophysics Data System (ADS)

    Wei, Aili; Liu, Xinghai; Shi, Quanxin; Liang, Wei

    2015-07-01

    Steel/Cu/Al laminated sheets were fabricated by two-pass hot rolling to improve the mechanical properties of steel/Al sheets. The bonding properties and deformability of the steel/Cu/Al sheets were studied. Steel/Al and steel/Cu/Al samples were rolled at 350°C for 15 min with the first-pass reduction of 40%, and then heated at 600°C for 5 min with different reductions. It was found that the steel/Cu/Al samples rolled by the second-pass reduction of 85% could endure the maximum 90° bend cycle times of 45, exhibiting excellent fatigue resistance as well as deformability. The steel/Al samples could only reach the maximum 90° bend cycle times of 20. Furthermore, the scanning electron microscope, energy-dispersive spectrometer, and electron backscattered diffraction results showed that the preferred growth orientations of Cu, Al4Cu9, and Al2Cu on the steel/Cu/Al laminated sheets are {-1, 1, 2} <1, -1, 1>, {1, 0, 0} <0, 1, 0> and {-1, 1, 2} <1, -1, 1> {1, 1, 0} <0, 0, 1>. The orientation relationships between Cu and Al2Cu are {1, 1, 0}(fcc)//{1, 1, 0}(bct) and {1, 1, 1}(fcc)//{1, 1, 1}(bct). The improved bonding property and excellent fatigue resistance as well as deformability were mainly ascribed to the tight combination and consistent deformability across steel, Al, and the transition layers (Cu, Al4Cu9, and Al2Cu).

  7. Cholesterol depletion by methyl-beta-cyclodextrin enhances myoblast fusion and induces the formation of myotubes with disorganized nuclei.

    PubMed

    Mermelstein, Cláudia S; Portilho, Débora M; Medeiros, Rommel B; Matos, Aline R; Einicker-Lamas, Marcelo; Tortelote, Giovane G; Vieyra, Adalberto; Costa, Manoel L

    2005-02-01

    The formation of a skeletal muscle fiber begins with the withdrawal of committed mononucleated precursors from the cell cycle. These myoblasts elongate while aligning with each other, guided by recognition between their membranes. This step is followed by cell fusion and the formation of long striated multinucleated myotubes. We used methyl-beta-cyclodextrin (MCD) in primary cultured chick skeletal muscle cells to deplete membrane cholesterol and investigate its role during myogenesis. MCD promoted a significant increase in the expression of troponin T, enhanced myoblast fusion, and induced the formation of large multinucleated myotubes with nuclei being clustered centrally and not aligned at the cell periphery. MCD myotubes were striated, as indicated by sarcomeric alpha-actinin staining, and microtubule and desmin filament distribution was not altered. Pre-fusion MCD-treated myoblasts formed large aggregates, with cadherin and beta-catenin being accumulated in cell adhesion contacts. We also found that the membrane microdomain marker GM1 was not present as clusters in the membrane of MCD-treated myoblasts. Our data demonstrate that cholesterol is involved in the early steps of skeletal muscle differentiation.

  8. Transforming growth factor-beta-induced stimulation of formation of collagen fiber network and anti-fibrotic effect of taurine in an in vitro model of hepatic fibrosis.

    PubMed

    Kato, Junya; Ido, Akio; Hasuike, Satoru; Uto, Hirofumi; Hori, Takeshi; Hayashi, Katsuhiro; Murakami, Shigeru; Terano, Akira; Tsubouchi, Hirohito

    2004-09-01

    The cell strain M, which was established from normal rat liver cells, is characterized by the active formation of a collagen fiber network. In this study, we investigated the characterization of M cells and evaluated the anti-fibrogenic effects of taurine using this culture system. M cells expressed cytokeratin (CK)8, CK18, vimentin, and alpha-smooth muscle actin, whereas expression of CK-19 or desmin was not detected. Also, M cells expressed transforming growth factor (TGF)-beta1, -beta2, and TGF-beta type I and II receptors, and treatment with TGF-beta1 (1ng/ml) for 6 days markedly stimulated the formation of a collagen fiber network and expression of procollagen alpha1(I) mRNA. When M cells were treated with various concentrations of taurine (10-50mM), network formation and procollagen alpha1(I) expression were significantly suppressed in a dose dependent manner. Additionally, even in the presence of TGF-beta1, taurine treatment effectively reduced the formation of a collagen fiber network. These results suggest that M cells exhibit features of not only hepatocytes but also myofibroblasts, and TGF-beta1 plays an important role in the formation of collagen fiber networks in this culture system. Additionally, this M cell culture system is appropriate for use as an in vitro model of hepatic fibrosis in the evaluation of the anti-fibrogenic effects of various agents.

  9. Driving Cartilage Formation in High-Density Human Adipose-Derived Stem Cell Aggregate and Sheet Constructs Without Exogenous Growth Factor Delivery

    PubMed Central

    Dang, Phuong N.; Solorio, Loran D.

    2014-01-01

    An attractive cell source for cartilage tissue engineering, human adipose-derived stem cells (hASCs) can be easily expanded and signaled to differentiate into chondrocytes. This study explores the influence of growth factor distribution and release kinetics on cartilage formation within 3D hASC constructs incorporated with transforming growth factor-β1 (TGF-β1)-loaded gelatin microspheres. The amounts of microspheres, TGF-β1 concentration, and polymer degradation rate were varied within hASC aggregates. Microsphere and TGF-β1 loading concentrations were identified that resulted in glycosaminoglycan (GAG) production comparable to those of control aggregates cultured in TGF-β1-containing medium. Self-assembling hASC sheets were then engineered for the production of larger, more clinically relevant constructs. Chondrogenesis was observed in hASC-only sheets cultured with exogenous TGF-β1 at 3 weeks. Importantly, sheets with incorporated TGF-β1-loaded microspheres achieved GAG production similar to sheets treated with exogenous TGF-β1. Cartilage formation was confirmed histologically via observation of cartilage-like morphology and GAG staining. This is the first demonstration of the self-assembly of hASCs into high-density cell sheets capable of forming cartilage in the presence of exogenous TGF-β1 or with TGF-β1-releasing microspheres. Microsphere incorporation may bypass the need for extended in vitro culture, potentially enabling hASC sheets to be implanted more rapidly into defects to regenerate cartilage in vivo. PMID:24873753

  10. Synthetic peptides corresponding to human follicle-stimulating hormone (hFSH)-beta-(1-15) and hFSH-beta-(51-65) induce uptake of 45Ca++ by liposomes: evidence for calcium-conducting transmembrane channel formation

    SciTech Connect

    Grasso, P.; Santa-Coloma, T.A.; Reichert, L.E. Jr. )

    1991-06-01

    We have previously described FSH receptor-mediated influx of 45Ca++ in cultured Sertoli cells from immature rats and receptor-enriched proteoliposomes via activation of voltage-sensitive and voltage-independent calcium channels. We have further shown that this effect of FSH does not require cholera toxin- or pertussis toxin-sensitive guanine nucleotide binding protein or activation of adenylate cyclase. In the present study, we have identified regions of human FSH-beta-subunit which appear to be involved in mediating calcium influx. We screened 11 overlapping peptide amides representing the entire primary structure of hFSH-beta-subunit for their effects on 45Ca++ flux in FSH receptor-enriched proteoliposomes. hFSH-beta-(1-15) and hFSH-beta-(51-65) induced uptake of 45Ca++ in a concentration-related manner. This effect of hFSH-beta-(1-15) and hFSH-beta-(51-65) was also observed in liposomes lacking incorporated FSH receptor. Reducing membrane fluidity by incubating liposomes (containing no receptor) with hFSH-beta-(1-15) or hFSH-beta-(51-65) at temperatures lower than the transition temperatures of their constituent phospholipids resulted in no significant (P greater than 0.05) difference in 45Ca++ uptake. The effectiveness of the calcium ionophore A23187, however, was abolished. Ruthenium red, a voltage-independent calcium channel antagonist, was able to completely block uptake of 45Ca++ induced by hFSH-beta-(1-15) and hFSH-beta-(51-65) whereas nifedipine, a calcium channel blocker specific for L-type voltage-sensitive calcium channels, was without effect. These results suggest that in addition to its effect on voltage-sensitive calcium channel activity, interaction of FSH with its receptor may induce formation of transmembrane aqueous channels which also facilitate influx of extracellular calcium.

  11. Isocholic acid formation from 7 alpha,12 alpha-dihydroxy-3-keto-5 beta-cholanoic acid with human liver enzyme.

    PubMed

    Amuro, Y; Yamade, W; Yamamoto, T; Kudo, K; Fujikura, M; Maebo, A; Hada, T; Higashino, K

    1986-12-01

    The formation of isocholic acid from 7 alpha, 12 alpha-dihydroxy-3-keto-5 beta-cholanoic acid by human liver preparations was examined in vitro. Liver preparations were incubated with 7 alpha, 12 alpha-dihydroxy-3-keto-5 beta-cholanoic acid at pH 7.4 in a phosphate buffer containing NADPH or NADH. The products formed were analyzed by gas chromatography and gas chromatography/mass spectrometry. Results showed that 7 alpha,12 alpha-dihydroxy-3-keto-5 beta-cholanoic acid was reduced mainly to isocholic acid and to cholic acid in a smaller amount in the presence of NADPH, while it was reduced only to cholic acid in the presence of NADH. The reducing enzyme participating in the formation of isocholic acid was localized largely in the cytosol and had more specificity to the unconjugated form as substrate than to the conjugated forms. 3-Keto bile acid analogues, 3-keto-5 beta-cholanoic and 7 alpha-hydroxy-3-keto-5 beta-cholanoic acids were not reduced to the corresponding iso-bile acids by the cytosol in the same conditions used in the isocholic acid formation and the activity of the enzyme catalyzing the reduction of 7 alpha,12 alpha-dihydroxy-3-keto-5 beta-cholanoic acid to isocholic acid was not inhibited by the addition of 3-keto-5 beta-cholanoic acid or 7 alpha-hydroxy-3-keto-5 beta-cholanoic acid to the reaction mixture. Furthermore, on column chromatography of Affi-Gel Blue, the peak of the enzyme catalyzing the reduction of 7 alpha,12 alpha-dihydroxy-3-keto-5 beta-cholanoic acid to isocholic acid was clearly distinguished from that of the enzyme catalyzing the reduction of 3-keto-5 beta-cholanoic acid to isolithocholic acid and that of alcohol dehydrogenase. These results indicate that this enzyme catalyzing the reduction of 7 alpha,12 alpha-dihydroxy-3-keto-5 beta-cholanoic acid to isocholic acid is different from the enzyme(s) catalyzing the reduction 3-keto-5 beta-cholanoic and 7 alpha-hydroxy-3-keto-5 beta-cholanoic acids to the corresponding iso-bile acids

  12. Formation of alpha and beta tantalum at the variation of magnetron sputtering conditions

    NASA Astrophysics Data System (ADS)

    Nasakina, E. O.; Sevostyanov, M. A.; Mikhaylova, A. B.; Baikin, A. S.; Sergienko, K. V.; Leonov, A. V.; Kolmakov, A. G.

    2016-02-01

    Nano- and microdimensional surface layers of α and β tantalum on flat NiTi, Ti, glass, etc. substrates were created. Structure and composition of samples were defined by SEM, AES and x-ray diffractometry. With increase in deposition time surface layer thickness not linearly increases. The transitional layer provide high adhesion of a surface layer to a substrate. Irrespective of summary sputtering time the β phase is formed in the beginning and at sputtering time more than 20 min on it α tantalum is deposited, while temperature remains below 150°C. Keywords: composite materials, surface layer, tantalum, alpha and beta phase, nitinol, corrosion resistance.

  13. Increased aerobic glycolysis through beta2 stimulation is a common mechanism involved in lactate formation during shock states.

    PubMed

    Levy, Bruno; Desebbe, Olivier; Montemont, Chantal; Gibot, Sebastien

    2008-10-01

    During septic shock, muscle produces lactate by way of an exaggerated NaK-adenosine triphosphatase (ATPase)-stimulated aerobic glycolysis associated with epinephrine stimulation possibly through beta2 adrenoreceptor involvement. It therefore seems logical that a proportion of hyperlactatemia in low cardiac output states would be also related to this mechanism. Thus, in low-flow and normal-to-high-flow models of shock, we investigate (1) whether muscle produces lactate and (2) whether muscle lactate production is linked to beta2 adrenergic stimulation and Na+K+-ATPase. We locally modulated the adrenergic pathway and Na+K+-ATPase activity in male Wistar rats' skeletal muscle using microdialysis with nonselective and selective beta blockers and ouabain in different models of rodent shock (endotoxin, peritonitis, and hemorrhage). Blood flow at the probe site was evaluated by ethanol clearance. We measured the difference between muscle lactate and blood lactate concentration, with a positive gradient indicating muscle lactate or pyruvate production. Epinephrine levels were elevated in all shock groups. All models were associated with hypotension and marked hyperlactatemia. Muscle lactate concentrations were consistently higher than arterial levels, with a mean gradient of 2.5+/-0.3 in endotoxic shock, 2.1+/-0.2 mM in peritonitis group, and 0.9+/-0.2 mM in hemorrhagic shock (P<0.05 for all groups). Muscle pyruvate concentrations were also always higher than arterial levels, with a mean gradient of 260+/-40 microM in endotoxic shock, 210+/-30 microM in peritonitis group, and 90+/-10 microM in hemorrhagic shock (P<0.05 for all groups). Despite a decrease in blood flow, lactate formation was decreased by all the pharmacological agents studied irrespective of shock mechanism. This demonstrates that lactate production during shock states is related, at least in part, to increased NaK-ATPase activity under beta2 stimulation. In shock state associated with a reduced or

  14. Formation of discontinuities and expansion waves in the outflow region of magnetic reconnection in an asymmetric current sheet

    NASA Astrophysics Data System (ADS)

    Lee, L. C.; Hsupeng, B. Y.; Lee, K. H.; Chao, J. K.

    2015-12-01

    The current sheets observed in the solar wind, magnetopause, and nightside plasma sheet can be asymmetric, in which the plasma densities and/or magnetic field magnitudes on the two sides of the current sheet are not equal. A hybrid code is used to simulate the 1-D Riemann problem for the generation and evolution of MHD discontinuities and expansion waves in the outflow region of magnetic reconnection in an asymmetric current sheet. In a symmetric current sheet, four types of compound structures are found: (a) RD-SS compound structure: show shock (SS) is attached to the downstream of rotational discontinuity (RD), (b) SS-RD: SS is followed by an adjacent RD, (c) SS-RD-SS: RD is trapped inside SS, and (d) switch-off slow shock (SSS). In the asymmetric current sheet, the rotational angle of magnetic field across an RD on the side with a higher plasma density is usually larger than that with a lower plasma density. In the asymmetric cases, a pure RD, a single SS, or a pure slow expansion wave (SE) may appear. When the asymmetry is further increased, RD may become absent in the low density side. For a highly asymmetric current sheet, a slow expansion wave (SE) is formed behind the SS-RD compound structure on the side with a very high plasma density.

  15. Direct Monitoring of β-Sheet Formation in the Outer Membrane Protein TtoA Assisted by TtOmp85.

    PubMed

    Henke, Katharina; Welte, Wolfram; Hauser, Karin

    2016-08-01

    Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy was applied to investigate the folding of an outer membrane protein, TtoA, assisted by TtOmp85, both from the thermophilic eubacterium Thermus thermophilus. To directly monitor the formation of β-sheet structure in TtoA and to analyze the function of TtOmp85, we immobilized unfolded TtoA on an ATR crystal. Interaction with TtOmp85 initiated TtoA folding as shown by time-dependent spectra recorded during the folding process. Our ATR-FTIR experiments prove that TtOmp85 possesses specific functionality to assist β-sheet formation of TtoA. We demonstrate the potential of this spectroscopic approach to study the interaction of outer membrane proteins in vitro and in a time-resolved manner. PMID:27400268

  16. Rubella - Fact Sheet for Parents

    MedlinePlus

    ... this page: About CDC.gov . Redirect for the Rubella fact sheet page. The current fact sheet can ... http://www.cdc.gov/vaccines/parents/diseases/child/rubella.html Print page Share Compartir File Formats Help: ...

  17. Beta-globin active chromatin Hub formation in differentiating erythroid cells and in p45 NF-E2 knock-out mice.

    PubMed

    Kooren, Jurgen; Palstra, Robert-Jan; Klous, Petra; Splinter, Erik; von Lindern, Marieke; Grosveld, Frank; de Laat, Wouter

    2007-06-01

    Expression of the beta-globin genes proceeds from basal to exceptionally high levels during erythroid differentiation in vivo. High expression is dependent on the locus control region (LCR) and coincides with more frequent LCR-gene contacts. These contacts are established in the context of an active chromatin hub (ACH), a spatial chromatin configuration in which the LCR, together with other regulatory sequences, loops toward the active beta-globin-like genes. Here, we used recently established I/11 cells as a model system that faithfully recapitulates the in vivo erythroid differentiation program to study the molecular events that accompany and underlie ACH formation. Upon I/11 cell induction, histone modifications changed, the ACH was formed, and the beta-globin-like genes were transcribed at rates similar to those observed in vivo. The establishment of frequent LCR-gene contacts coincided with a more efficient loading of polymerase onto the beta-globin promoter. Binding of the transcription factors GATA-1 and EKLF to the locus, although previously shown to be required, was not sufficient for ACH formation. Moreover, we used knock-out mice to show that the erythroid transcription factor p45 NF-E2, which has been implicated in beta-globin gene regulation, is dispensable for beta-globin ACH formation.

  18. Inhibition of beta-amyloid aggregation by fluorescent dye labels

    SciTech Connect

    Amaro, Mariana; Wellbrock, Thorben; Birch, David J. S.; Rolinski, Olaf J.

    2014-02-10

    The fluorescence decay of beta-amyloid's (Aβ) intrinsic fluorophore tyrosine has been used for sensing the oligomer formation of dye-labelled Aβ monomers and the results compared with previously studied oligomerization of the non-labelled Aβ peptides. It has been demonstrated that two different sized, covalently bound probes 7-diethylaminocoumarin-3-carbonyl and Hilyte Fluor 488 (HLF), alter the rate and character of oligomerization to different extents. The ability of HLF to inhibit formation of highly ordered structures containing beta-sheets was also shown. The implications of our findings for using fluorescence methods in amyloidosis research are discussed and the advantages of this auto-fluorescence approach highlighted.

  19. Inhibition of beta-amyloid aggregation by fluorescent dye labels

    NASA Astrophysics Data System (ADS)

    Amaro, Mariana; Wellbrock, Thorben; Birch, David J. S.; Rolinski, Olaf J.

    2014-02-01

    The fluorescence decay of beta-amyloid's (Aβ) intrinsic fluorophore tyrosine has been used for sensing the oligomer formation of dye-labelled Aβ monomers and the results compared with previously studied oligomerization of the non-labelled Aβ peptides. It has been demonstrated that two different sized, covalently bound probes 7-diethylaminocoumarin-3-carbonyl and Hilyte Fluor 488 (HLF), alter the rate and character of oligomerization to different extents. The ability of HLF to inhibit formation of highly ordered structures containing beta-sheets was also shown. The implications of our findings for using fluorescence methods in amyloidosis research are discussed and the advantages of this auto-fluorescence approach highlighted.

  20. Hydrogen-1, carbon-13, and nitrogen-15 NMR spectroscopy of Anabaena 7120 flavodoxin: Assignment of. beta. -sheet and flavin binding site resonances and analysis of protein-flavin interactions

    SciTech Connect

    Stockman, B.J.; Krezel, A.M.; Markley, J.L. ); Leonhardt, K.G.; Straus, N.A. )

    1990-10-01

    Sequence-specific {sup 1}H and {sup 13}C NMR assignments have been made for residues that form the five-stranded parallel {beta}-sheet and the flavin mononucleotide (FMN) binding site of oxidized Anabaena 7120 flavodoxin. Interstrand nuclear Overhauser enhancements (NOEs) indicate that the {beta}-sheet arrangement is similar to that observed in the crystal structure of the 70% homologous long-chain flavodoxin from Anacystis nidulans. A total of 62 NOEs were identified: 8 between protons of bound FMN, 29 between protons of the protein in the flavin binding site, and 25 between protons of bound FMN and protons of the protein. These constraints were used to determine the localized solution structure of the FMN binding site. The electronic environment and conformation of the protein-bound flavin isoalloxazine ring were investigated by determining {sup 13}C-{sup 1}H coupling constants. The carbonyl edge of the flavin ring was found to be slightly polarized. The xylene ring was found to be nonplanar. Tyrosine 94, located adjacent to the flavin isoalloxazine ring, was shown to have a hindered aromatic ring flip rate.

  1. Formation of high-{beta} plasma and stable confinement of toroidal electron plasma in Ring Trap 1

    SciTech Connect

    Saitoh, H.; Yoshida, Z.; Morikawa, J.; Furukawa, M.; Yano, Y.; Kawai, Y.; Kobayashi, M.; Vogel, G.; Mikami, H.

    2011-05-15

    Formation of high-{beta} electron cyclotron resonance heating plasma and stable confinement of pure electron plasma have been realized in the Ring Trap 1 device, a magnetospheric configuration generated by a levitated dipole field magnet. The effects of coil levitation resulted in drastic improvements of the confinement properties, and the maximum local {beta} value has exceeded 70%. Hot electrons are major component of electron populations, and its particle confinement time is 0.5 s. Plasma has a peaked density profile in strong field region [H. Saitoh et al., 23rd IAEA Fusion Energy Conference EXC/9-4Rb (2010)]. In pure electron plasma experiment, inward particle diffusion is realized, and electrons are stably trapped for more than 300 s. When the plasma is in turbulent state during beam injection, plasma flow has a shear, which activates the diocotron (Kelvin-Helmholtz) instability. The canonical angular momentum of the particle is not conserved in this phase, realizing the radial diffusion of charged particles across closed magnetic surfaces. [Z. Yoshida et al., Phys Rev. Lett. 104, 235004 (2010); H. Saitoh et al., Phys. Plasmas 17, 112111 (2010).].

  2. Formation and accumulation of alpha-acids, beta-acids, desmethylxanthohumol, and xanthohumol during flowering of hops (Humulus lupulus L.).

    PubMed

    De Keukeleire, Jelle; Ooms, Geert; Heyerick, Arne; Roldan-Ruiz, Isabel; Van Bockstaele, Erik; De Keukeleire, Denis

    2003-07-16

    Important secondary metabolites, present in hops (Humulus lupulus L.), include alpha-acids and beta-acids, which are essential for the brewing of beer, as well as the prenylated chalcones, desmethylxanthohumol, and xanthohumol, which exhibit interesting bioactive properties. Their formation and accumulation in five selected hop varieties, Wye Challenger, Wye Target, Golding, Admiral, and Whitbread Golding Variety, were quantitatively monitored by high-performance liquid chromatography using UV detection. All target compounds were present from the onset of flowering, not only in female hop cones but also in male inflorescences, albeit in low concentrations. During development from female inflorescences to cones, levels of alpha-acids, beta-acids, desmethylxanthohumol, and xanthohumol gradually increased, while each hop variety exhibited individual accumulation rates. Furthermore, these compounds were present in leaves of fully grown hops as well. The study demonstrated that key compounds for flavor and potential beneficial health effects associated with beer not only reside in the glandular lupulin structures but also are distributed over various parts of the hop plant. PMID:12848522

  3. The influence of beta subunit structure on the interaction of Na+/K(+)-ATPase complexes with Na+. A chimeric beta subunit reduces the Na+ dependence of phosphoenzyme formation from ATP.

    PubMed

    Eakle, K A; Lyu, R M; Farley, R A

    1995-06-01

    High-affinity ouabain binding to Na+/K(+)-ATPase (sodium- and potassium-transport adenosine triphosphatase (EC 3.6.1.37)) requires phosphorylation of the alpha subunit of the enzyme either by ATP or by inorganic phosphate. For the native enzyme (alpha/beta 1), the ATP-dependent reaction proceeds about 4-fold more slowly in the absence of Na+ than when saturating concentrations of Na+ are present. Hybrid pumps were formed from either the alpha 1 or the alpha 3 subunit isoforms of Na+/K(+)-ATPase and a chimeric beta subunit containing the transmembrane segment of the Na+/K(+)-ATPase beta 1 isoform and the external domain of the gastric H+/K(+)-ATPase beta subunit (alpha/NH beta 1 complexes). In the absence of Na+, these complexes show a rate of ATP-dependent ouabain binding from approximately 75-100% of the rate seen in the presence of Na+ depending on buffer conditions. Nonhydrolyzable nucleotides or treatment of ATP with apyrase abolishes ouabain binding, demonstrating that ouabain binding to alpha/NH beta 1 complexes requires phosphorylation of the protein. Buffer ions inhibit ouabain binding by alpha/NH beta 1 in the absence of Na+ rather than promote ouabain binding, indicating that they are not substituting for sodium ions in the phosphorylation reaction. The pH dependence of ATP-dependent ouabain binding in the presence or absence of Na+ is similar, suggesting that protons are probably not substituting for Na+. Hybrid alpha/NH beta 1 pumps also show slightly higher apparent affinities (2-3-fold) for ATP, Na+, and ouabain; however, these are not sufficient to account for the increase in ouabain binding in the absence of Na+. In contrast to phosphoenzyme formation and ouabain binding by alpha/NH beta 1 complexes in the absence of Na+, ATPase activity, measured as release of phosphate from ATP, requires Na+. These data suggest that the transition from E1P to E2P during the catalytic cycle does not occur when the sodium binding sites are not occupied. Thus, the

  4. Transforming growth factor-beta 1 (TGF-beta1) prevents the age-dependent decrease in bone formation in human osteoblast/implant cultures.

    PubMed

    Zhang, Hai; Aronow, Michael S; Gronowicz, Gloria A

    2005-10-01

    Titanium implants have been extensively used in orthopedic surgery and dentistry. Most of the patients who receive such implants are elderly with a compromised ability to heal and form new bone. By using an in vitro osteoblast/implant culture system, the potency of TGF-beta1 in enhancing mineralization of human osteoblast cultures from elderly subjects was investigated in this study. Primary human osteoblast (HOB) cells obtained from different age group human subjects [Young (Y), Middle (M), and Old (O)] were cultured on Ti alloy (Ti-6Al-4V) disks with or without continuous administration of 0.2 ng/mL TGF-beta1 in the medium for 2 or 4 weeks. TGF-beta1 significantly (p < 0.05) increased calcium content and the size of calcified nodules on implant disks in the O group, but had no effect on the Y or M groups. The number of calcified nodules was not different with or without TGF-beta1 in all age groups. As measured by Northern blot analysis and RT-PCR, TGF-beta1 significantly increased the expression of bone-specific extracellular matrix proteins, including alkaline phosphatase, Type I collagen, bone sialoprotein and osteocalcin, after both 2 and 4 weeks in the O group but not in the Y group. In conclusion, TGF-beta1 enhances mineralization on implant materials of osteoblast cultures from elderly human subjects.

  5. Pattern formation in icosahedral virus capsids: the papova viruses and Nudaurelia capensis beta virus.

    PubMed Central

    Marzec, C J; Day, L A

    1993-01-01

    The capsids of the spherical viruses all show underlying icosahedral symmetry, yet they differ markedly in capsomere shape and in capsomere position and orientation. The capsid patterns presented by the capsomere shapes, positions, and orientations of three viruses (papilloma, SV40, and N beta V) have been generated dynamically through a bottom-up procedure which provides a basis for understanding the patterns. A capsomere shape is represented in two-dimensional cross-section by a mass or charge density on the surface of a sphere, given by an expansion in spherical harmonics, and referred to herein as a morphological unit (MU). A capsid pattern is represented by an icosahedrally symmetrical superposition of such densities, determined by the positions and orientations of its MUs on the spherical surface. The fitness of an arrangement of MUs is measured by an interaction integral through which all capsid elements interact with each other via an arbitrary function of distance. A capsid pattern is generated by allowing the correct number of approximately shaped MUs to move dynamically on the sphere, positioning themselves until an extremum of the fitness function is attained. The resulting patterns are largely independent of the details of both the capsomere representation and the interaction function; thus the patterns produced are generic. The simplest useful fitness function is sigma 2, the average square of the mass (or charge) density, a minimum of which corresponds to a "uniformly spaced" MU distribution; to good approximation, the electrostatic free energy of charged capsomeres, calculated from the linearized Poisson-Boltzmann equation, is proportional to sigma 2. With disks as MUs, the model generates the coordinated lattices familiar from the quasi-equivalence theory, indexed by triangulation numbers. Using fivefold MUs, the model generates the patterns observed at different radii within the T = 7 capsid of papilloma and at the surface of SV40; threefold MUs

  6. A forkhead gene related to HNF-3beta is required for gastrulation and axis formation in the ascidian embryo.

    PubMed

    Olsen, C L; Jeffery, W R

    1997-09-01

    We have isolated a member of the HNF-3/forkhead gene family in ascidians as a means to determine the role of winged-helix genes in chordate development. The MocuFH1 gene, isolated from a Molgula oculata cDNA library, exhibits a forkhead DNA-binding domain most similar to zebrafish axial and rodent HNF-3beta. MocuFH1 is a single copy gene but there is at least one other related forkhead gene in the M. oculata genome. The MocuFH1 gene is expressed in the presumptive endoderm, mesenchyme and notochord cells beginning during the late cleavage stages. During gastrulation, MocuFH1 expression occurs in the prospective endoderm cells, which invaginate at the vegetal pole, and in the presumptive notochord and mesenchyme cells, which involute over the anterior and lateral lips of the blastopore, respectively. However, this gene is not expressed in the presumptive muscle cells, which involute over the posterior lip of the blastopore. MocuFH1 expression continues in the same cell lineages during neurulation and axis formation, however, during the tailbud stage, MocuFH1 is also expressed in ventral cells of the brain and spinal cord. The functional role of the MocuFH1 gene was studied using antisense oligodeoxynucleotides (ODNs), which transiently reduce MocuFH1 transcript levels during gastrulation. Embryos treated with antisense ODNs cleave normally and initiate gastrulation. However, gastrulation is incomplete, some of the endoderm and notochord cells do not enter the embryo and undergo subsequent movements, and axis formation is abnormal. In contrast, the prospective muscle cells, which do not express MocuFH1, undergo involution and later express muscle actin and acetylcholinesterase, markers of muscle cell differentiation. The results suggest that MocuFH1 is required for morphogenetic movements of the endoderm and notochord precursor cells during gastrulation and axis formation. The effects of inhibiting MocuFH1 expression on embryonic axis formation in ascidians are

  7. Sub-100 nm Si nanowire and nano-sheet array formation by MacEtch using a non-lithographic InAs nanowire mask

    NASA Astrophysics Data System (ADS)

    Shin, Jae Cheol; Zhang, Chen; Li, Xiuling

    2012-08-01

    We report a non-lithographical method for the fabrication of ultra-thin silicon (Si) nanowire (NW) and nano-sheet arrays through metal-assisted-chemical-etching (MacEtch) with gold (Au). The mask used for metal patterning is a vertical InAs NW array grown on a Si substrate via catalyst-free, strain-induced, one-dimensional heteroepitaxy. Depending on the Au evaporation angle, the shape and size of the InAs NWs are transferred to Si by Au-MacEtch as is (NWs) or in its projection (nano-sheets). The Si NWs formed have diameters in the range of ˜25-95 nm, and aspect ratios as high as 250 in only 5 min etch time. The formation process is entirely free of organic chemicals, ensuring pristine Au-Si interfaces, which is one of the most critical requirements for high yield and reproducible MacEtch.

  8. Sub-100 nm Si nanowire and nano-sheet array formation by MacEtch using a non-lithographic InAs nanowire mask.

    PubMed

    Shin, Jae Cheol; Zhang, Chen; Li, Xiuling

    2012-08-01

    We report a non-lithographical method for the fabrication of ultra-thin silicon (Si) nanowire (NW) and nano-sheet arrays through metal-assisted-chemical-etching (MacEtch) with gold (Au). The mask used for metal patterning is a vertical InAs NW array grown on a Si substrate via catalyst-free, strain-induced, one-dimensional heteroepitaxy. Depending on the Au evaporation angle, the shape and size of the InAs NWs are transferred to Si by Au-MacEtch as is (NWs) or in its projection (nano-sheets). The Si NWs formed have diameters in the range of ∼25-95 nm, and aspect ratios as high as 250 in only 5 min etch time. The formation process is entirely free of organic chemicals, ensuring pristine Au-Si interfaces, which is one of the most critical requirements for high yield and reproducible MacEtch. PMID:22781145

  9. Influence of Interleukin-1 Beta on Platelet-Poor Plasma Clot Formation: A Potential Impact on Early Bone Healing

    PubMed Central

    Masci, Paul P.; Crawford, Ross; Xiao, Yin

    2016-01-01

    Objectives Hematoma quality (especially the fibrin matrix) plays an important role in the bone healing process. Here, we investigated the effect of interleukin-1 beta (IL-1β) on fibrin clot formation from platelet-poor plasma (PPP). Methods Five-milliliter of rat whole-blood samples were collected from the hepatic portal vein. All blood samples were firstly standardized via a thrombelastograph (TEG), blood cell count, and the measurement of fibrinogen concentration. PPP was prepared by collecting the top two-fifths of the plasma after centrifugation under 400 × g for 10 min at 20°C. The effects of IL-1β cytokines on artificial fibrin clot formation from PPP solutions were determined by scanning electronic microscopy (SEM), confocal microscopy (CM), turbidity, and clot lysis assays. Results The lag time for protofibril formation was markedly shortened in the IL-1β treatment groups (243.8 ± 76.85 in the 50 pg/mL of IL-1β and 97.5 ± 19.36 in the 500 pg/mL of IL-1β) compared to the control group without IL-1β (543.8 ± 205.8). Maximal turbidity was observed in the control group. IL-1β (500 pg/mL) treatment significantly decreased fiber diameters resulting in smaller pore sizes and increased density of the fibrin clot structure formed from PPP (P < 0.05). The clot lysis assay revealed that 500 pg/mL IL-1β induced a lower susceptibility to dissolution due to the formation of thinner and denser fibers. Conclusion IL-1β can significantly influence PPP fibrin clot structure, which may affect the early bone healing process. PMID:26909757

  10. Natalizumab plus interferon beta-1a reduces lesion formation in relapsing multiple sclerosis.

    PubMed

    Radue, Ernst-Wilhelm; Stuart, William H; Calabresi, Peter A; Confavreux, Christian; Galetta, Steven L; Rudick, Richard A; Lublin, Fred D; Weinstock-Guttman, Bianca; Wynn, Daniel R; Fisher, Elizabeth; Papadopoulou, Athina; Lynn, Frances; Panzara, Michael A; Sandrock, Alfred W

    2010-05-15

    The SENTINEL study showed that the addition of natalizumab improved outcomes for patients with relapsing multiple sclerosis (MS) who had experienced disease activity while receiving interferon beta-1a (IFNbeta-1a) alone. Previously unreported secondary and tertiary magnetic resonance imaging (MRI) measures are presented here. Patients received natalizumab 300 mg (n=589) or placebo (n=582) intravenously every 4 weeks plus IFNbeta-1a 30 microg intramuscularly once weekly. Annual MRI scans allowed comparison of a range of MRI end points versus baseline. Over 2 years, 67% of patients receiving natalizumab plus IFNbeta-1a remained free of new or enlarging T2-lesions compared with 30% of patients receiving IFNbeta-1a alone. The mean change from baseline in T2 lesion volume over 2 years decreased in patients receiving natalizumab plus IFNbeta-1a and increased in those receiving IFNbeta-1a alone (-277.5mm(3) versus 525.6mm(3); p<0.001). Compared with IFNbeta-1a alone, add-on natalizumab therapy resulted in a smaller increase in mean T1-hypointense lesion volume after 2 years (1821.3mm(3) versus 2210.5mm(3); p<0.001), a smaller mean number of new T1-hypointense lesions over 2 years (2.3 versus 4.1; p<0.001), and a slower rate of brain atrophy during the second year of therapy (-0.31% versus -0.40%; p=0.020). Natalizumab add-on therapy reduced gadolinium-enhancing, T1-hypointense, and T2 MRI lesion activity and slowed brain atrophy progression in patients with relapsing MS who experienced disease activity despite treatment with IFNbeta-1a alone. PMID:20236661

  11. Effects of transforming growth factor beta and epidermal growth factor on cell proliferation and the formation of bone nodules in isolated fetal rat calvaria cells.

    PubMed

    Antosz, M E; Bellows, C G; Aubin, J E

    1989-08-01

    When cells enzymatically isolated from fetal rat calvaria (RC cells) are cultured in vitro in the presence of ascorbic acid and Na beta-glycerophosphate, discrete three-dimensional nodules form with the histologic, immunohistochemical, and ultrastructural characteristics of bone (Bellows et al; Calcified Tissue International 38:143-154, 1986; Bhargava et al., Bone, 9:155-163, 1988). Quantitation of the number of bone nodules that forms provides a colony assay for osteoprogenitor cells present in the RC population (Bellows and Aubin, Develop. Biol., 133:8-13, 1989). Continuous culture with either epidermal growth factor (EGF) or transforming growth factor beta (TGF-beta) results in dose-dependent inhibition of bone nodule formation; however, the former causes increased proliferation and saturation density, while the latter reduces both parameters. Addition of EGF (48 h pulse, 2-200 ng/ml) to RC cells at day 1 after plating results in increased proliferation and population saturation density and an increased number of bone nodules formed. Similar pulses at confluence and in postconfluent multilayered cultures when nodules first begin forming (approx. day 11) inhibited bone nodule formation and resulted in a smaller stimulation of cell proliferation. Forty-eight hour pulses of TGF-beta (0.01-1 ng/ml) reduced bone nodule formation and proliferation at all times examined, with pulses on day 1 causing maximum inhibition. The effects of pulses with TGF-beta and EGF on inhibition of nodule formation are independent of the presence of serum in the culture medium during the pulse. The data suggest that whereas EGF can either stimulate or inhibit the formation of bone nodules depending upon the time and duration of exposure, TGF-B inhibits bone nodule formation under all conditions tested. Moreover, these effects on osteoprogenitor cell differentiation do not always correlate with the effects of the growth factors on RC cell proliferation. PMID:2787326

  12. Metal ion-dependent, reversible, protein filament formation by designed beta-roll polypeptides

    PubMed Central

    Scotter, Andrew J; Guo, Meng; Tomczak, Melanie M; Daley, Margaret E; Campbell, Robert L; Oko, Richard J; Bateman, David A; Chakrabartty, Avijit; Sykes, Brian D; Davies, Peter L

    2007-01-01

    Background A right-handed, calcium-dependent β-roll structure found in secreted proteases and repeat-in-toxin proteins was used as a template for the design of minimal, soluble, monomeric polypeptides that would fold in the presence of Ca2+. Two polypeptides were synthesised to contain two and four metal-binding sites, respectively, and exploit stacked tryptophan pairs to stabilise the fold and report on the conformational state of the polypeptide. Results Initial analysis of the two polypeptides in the presence of calcium suggested the polypeptides were disordered. The addition of lanthanum to these peptides caused aggregation. Upon further study by right angle light scattering and electron microscopy, the aggregates were identified as ordered protein filaments that required lanthanum to polymerize. These filaments could be disassembled by the addition of a chelating agent. A simple head-to-tail model is proposed for filament formation that explains the metal ion-dependency. The model is supported by the capping of one of the polypeptides with biotin, which disrupts filament formation and provides the ability to control the average length of the filaments. Conclusion Metal ion-dependent, reversible protein filament formation is demonstrated for two designed polypeptides. The polypeptides form filaments that are approximately 3 nm in diameter and several hundred nm in length. They are not amyloid-like in nature as demonstrated by their behaviour in the presence of congo red and thioflavin T. A capping strategy allows for the control of filament length and for potential applications including the "decoration" of a protein filament with various functional moieties. PMID:17908326

  13. alpha,beta-Dehydro-3,4-dihydroxyphenylalanine derivatives: rate and mechanism of formation.

    PubMed

    Rzepecki, L M; Waite, J H

    1991-02-15

    The amino acid L-3,4-dihydroxyphenylalanine (DOPA), when present in the primary sequence of proteins, does not form melanin upon oxidation to the quinone, since its amine moiety participates in a peptide bond and cannot undergo internal cyclization. Instead, peptidyl DOPA quinone is available for other reactions. We have investigated the oxidation chemistry of a low molecular weight peptidyl DOPA analog, N-acetylDOPA ethyl ester (NAcDEE), and have shown that a major product of oxidation is an unsaturated DOPA derivative, N-acetyl-alpha,beta-dehydroDOPA ethyl ester (NAc delta DEE) (see companion paper, Rzepecki et al., Arch. Biochem. Biophys. (1991) 285, 17-26). In the present study, we have explored kinetic and mechanistic features of the conversion of NAcDEE to NAc delta DEE and found that the reaction requires: (i) oxidation of NAcDEE to the quinone, (ii) the presence of a Lewis base as a catalyst (phosphate anion was the best of those tried in the pH range 6.0-8.0), and (iii) prevention of competing reactions such as Michael additions. Conversion efficiencies in the presence of Lewis bases ranged between 12 and 19% at pH 8.0 and 35 and 90% at pH 6.0. At least two separate reaction mechanisms appeared necessary to explain the kinetic data: (i) a pseudo-first-order mechanism at pH 6.0 and above, and (ii) an additional second-order mechanism at higher pH which involved both NAcDEE catechol and quinone. The apparent pseudo-first-order rate constants increased with pH from 2.36 X 10(-4) s-1 at pH 6.0 to about 30 X 10(-4) s-1 at pH 8.0 in 0.1 M sodium phosphate. Tautomerization of DOPA quinone to dehydroDOPA may thus be a factor in the sclerotization of natural structures incorporating DOPA containing proteins. PMID:1899328

  14. Formation of fluorescent proteins by the attachment of phycoerythrobilin to R-phycoerythrin alpha and beta apo-subunits.

    PubMed

    Isailovic, Dragan; Sultana, Ishrat; Phillips, Gregory J; Yeung, Edward S

    2006-11-01

    Formation of fluorescent proteins was explored after incubation of recombinant apo-subunits of phycobiliprotein R-phycoerythrin with phycoerythrobilin chromophore. Alpha and beta apo-subunit genes of R-phycoerythrin from red algae Polisiphonia boldii were cloned in plasmid pET-21d(+). Hexahistidine-tagged alpha and beta apo-subunits were expressed in Escherichia coli. Although expressed apo-subunits formed inclusion bodies, fluorescent holo-subunits were constituted after incubation of E. coli cells with phycoerythrobilin. Holo-subunits contained both phycoerythrobilin and urobilin chromophores. Fluorescence and differential interference contrast microscopy showed polar location of holo-subunit inclusion bodies in bacterial cells. Cells containing fluorescent holo-subunits were several times brighter than control cells as found by fluorescence microscopy and flow cytometry. The addition of phycoerythrobilin to cells did not show cytotoxic effects, in contrast to expression of proteins in inclusion bodies. In an attempt to improve solubility, R-phycoerythrin apo-subunits were fused to maltose-binding protein and incubated with phycoerythrobilin both in vitro and in vivo. Highly fluorescent soluble fusion proteins containing phycoerythrobilin as the sole chromophore were formed. Fusion proteins were localized by fluorescence microscopy either throughout E. coli cells or at cell poles. Flow cytometry showed that cells containing fluorescent fusion proteins were up to 10 times brighter than control cells. Results indicate that fluorescent proteins formed by attachment of phycoerythrobilin to expressed apo-subunits of phycobiliproteins can be used as fluorescent probes for analysis of cells by microscopy and flow cytometry. A unique property of these fluorescent reporters is their utility in both properly folded (soluble) subunits and subunits aggregated in inclusion bodies.

  15. Beta-radiation-induced resistance to MNNG initiation of papilloma but not carcinoma formation in mouse skin

    SciTech Connect

    Mitchel, R.E.; Gragtmans, N.J.; Morrison, D.P. )

    1990-02-01

    We have shown previously that the risk of tumor initiation, promotion, and progression in animals initiated with alkylating agents can be drastically altered by hyperthermia treatments. We show here that ionizing radiation can also alter the risk of tumor initiation by alkylating agents. Using a two-step skin tumorigenesis protocol in female SENCAR mice (initiation by MNNG, promotion with TPA), we exposed the dorsal skin of the mice to various doses of 90Sr/90Y beta radiation near the time of initiation. The radiation produced a dose-dependent reduction in the number of papillomas which appeared after TPA promotion, with about a 20% reduction in animals receiving 0.5 Gy surface dose just before initiation, about 50% reduction after 2.5 Gy, and greater than 80% at doses above 5 Gy. A dose of 2.5 Gy in animals initiated with DMBA produced no significant reduction. One skin hyperthermia treatment along with radiation in MNNG-initiated animals partially blocked the protective effect of radiation and increased the papilloma frequency. Radiation (2.5 Gy) given either 6 days before or after MNNG initiation was less effective but still reduced papilloma frequency about 20%. In sharp contrast to the marked reduction in papilloma formation, these same animals showed no change in carcinoma frequency with any of the doses or schedules of beta radiation. MNNG initiation alone produced three types of initiated cells. One type, produced in low yield, was promotion-independent with a high probability of progression to a carcinoma and appeared unaffected by the radiation. A second type, produced in intermediate yield, was promotion-dependent and also had a high progression probability, but was likewise unaffected by the radiation. The third and most abundant type was promotion-dependent with a very low progression probability.

  16. FORMATION OF FLUORESCENT PROTEINS BY THE ATTACHMENT OF PHYCOERYTHROBILIN TO R-PHYCOERYTHRIN ALPHA AND BETA APO-SUBUNITS

    PubMed Central

    Isailovic, Dragan; Sultana, Ishrat; Phillips, Gregory J.; Yeung, Edward S.

    2006-01-01

    Formation of fluorescent proteins was explored after incubation of recombinant apo-subunits of phycobiliprotein R-phycoerythrin with phycoerythrobilin chromophore. Alpha and beta apo-subunit genes of R-phycoerythrin from red algae Polisiphonia boldii were cloned in plasmids pET-21d (+). Hexa-histidine tagged apo-alpha and apo-beta subunits were expressed in Escherichia coli. Although expressed apo-subunits formed inclusion bodies, fluorescent holo-subunits were constituted after incubation of Escherichia coli cells with phycoerythrobilin. Subunits contained both phycoerythrobilin and urobilin chromophores. Fluorescence and differential interference contrast microscopy showed polar location of holo-subunit inclusion bodies in bacterial cells. Cells containing fluorescent holo-subunits were several times brighter than control cells as found by fluorescence microscopy and flow cytometry. Addition of phycoerythrobilin to cells did not show cytotoxic effects in contrast to expression of proteins in inclusion bodies. In an attempt to improve solubility, R-phycoerythrin apo-subunits were fused to maltose binding protein and incubated with phycoerythrobilin both in vitro and in vivo. Highly-fluorescent soluble fusion proteins were formed containing phycoerythrobilin as the sole chromophore. Fusion proteins were localized by fluorescence microscopy either throughout Escherichia coli cells or at cell poles. Flow cytometry showed that cells containing fluorescent fusion proteins were up to ten times brighter than control cells. Results indicate that fluorescent proteins formed by attachment of phycoerythrobilin to expressed apo-subunits of phycobiliproteins can be used as fluorescent probes for analysis of cells by microscopy and flow cytometry. A unique property of these fluorescent reporters is their utility in both properly folded (soluble) subunits and subunits aggregated in inclusion bodies. PMID:16979575

  17. Molecular basis of transmembrane beta-barrel formation of staphylococcal pore-forming toxins.

    PubMed

    Yamashita, Daichi; Sugawara, Takaki; Takeshita, Miyu; Kaneko, Jun; Kamio, Yoshiyuki; Tanaka, Isao; Tanaka, Yoshikazu; Yao, Min

    2014-01-01

    Pathogenic bacteria secrete pore-forming toxins (PFTs) to attack target cells. PFTs are expressed as water-soluble monomeric proteins, which oligomerize into nonlytic prepore intermediates on the target cell membrane before forming membrane-spanning pores. Despite a wealth of biochemical data, the lack of high-resolution prepore structural information has hampered understanding of the β-barrel formation process. Here, we report crystal structures of staphylococcal γ-haemolysin and leucocidin prepores. The structures reveal a disordered bottom half of the β-barrel corresponding to the transmembrane region, and a rigid upper extramembrane half. Spectroscopic analysis of fluorescently labelled mutants confirmed that the prepore is distinct from the pore within the transmembrane region. Mutational analysis also indicates a pivotal role for the glycine residue located at the lipid-solvent interface as a 'joint' between the two halves of the β-barrel. These observations suggest a two-step transmembrane β-barrel pore formation mechanism in which the upper extramembrane and bottom transmembrane regions are formed independently. PMID:25263813

  18. Effect of tetracyclines on the dynamics of formation and destructuration of beta2-microglobulin amyloid fibrils.

    PubMed

    Giorgetti, Sofia; Raimondi, Sara; Pagano, Katiuscia; Relini, Annalisa; Bucciantini, Monica; Corazza, Alessandra; Fogolari, Federico; Codutti, Luca; Salmona, Mario; Mangione, Palma; Colombo, Lino; De Luigi, Ada; Porcari, Riccardo; Gliozzi, Alessandra; Stefani, Massimo; Esposito, Gennaro; Bellotti, Vittorio; Stoppini, Monica

    2011-01-21

    The discovery of methods suitable for the conversion in vitro of native proteins into amyloid fibrils has shed light on the molecular basis of amyloidosis and has provided fundamental tools for drug discovery. We have studied the capacity of a small library of tetracycline analogues to modulate the formation or destructuration of β2-microglobulin fibrils. The inhibition of fibrillogenesis of the wild type protein was first established in the presence of 20% trifluoroethanol and confirmed under a more physiologic environment including heparin and collagen. The latter conditions were also used to study the highly amyloidogenic variant, P32G. The NMR analysis showed that doxycycline inhibits β2-microglobulin self-association and stabilizes the native-like species through fast exchange interactions involving specific regions of the protein. Cell viability assays demonstrated that the drug abolishes the natural cytotoxic activity of soluble β2-microglobulin, further strengthening a possible in vivo therapeutic exploitation of this drug. Doxycycline can disassemble preformed fibrils, but the IC(50) is 5-fold higher than that necessary for the inhibition of fibrillogenesis. Fibril destructuration is a dynamic and time-dependent process characterized by the early formation of cytotoxic protein aggregates that, in a few hours, convert into non-toxic insoluble material. The efficacy of doxycycline as a drug against dialysis-related amyloidosis would benefit from the ability of the drug to accumulate just in the skeletal system where amyloid is formed. In these tissues, the doxycycline concentration reaches values several folds higher than those resulting in inhibition of amyloidogenesis and amyloid destructuration in vitro. PMID:21068391

  19. Development of an ultra-high-temperature process for the enzymatic hydrolysis of lactose: II. Oligosaccharide formation by two thermostable beta-glycosidases.

    PubMed

    Petzelbauer, I; Zeleny, R; Reiter, A; Kulbe, K D; Nidetzky, B

    2000-07-20

    During lactose conversion at 70 degrees C, when catalyzed by beta-glycosidases from the archea Sulfolobus solfataricus (SsbetaGly) and Pyrococcus furiosus (CelB), galactosyl transfer to acceptors other than water competes efficiently with complete hydrolysis of substrate. This process leads to transient formation of a range of new products, mainly disaccharides and trisaccharides, and shows a marked dependence on initial substrate concentration and lactose conversion. Oligosaccharides have been analyzed quantitatively by using capillary electrophoresis and high performance anion-exchange chromatography. At 270 g/L initial lactose, they accumulate at a maximum concentration of 86 g/L at 80% lactose conversion. With both enzymes, the molar ratio of trisaccharides to disaccharides is maximal at an early stage of reaction and decreases directly proportional to increasing substrate conversion. Overall, CelB produces about 6% more hydrolysis byproducts than SsbetaGly. However, the product spectrum of SsbetaGly is richer in trisaccharides, and this agrees with results obtained from the steady-state kinetics analyses of galactosyl transfer catalyzed by SsbetaGly and CelB. The major transgalactosylation products of SsbetaGly and CelB have been identified. They are beta-D-Galp-(1-->3)-Glc and beta-D-Galp-(1-->6)-Glc, and beta-D-Galp-(1-->3)-lactose and beta-D-Galp-(1-->6)-lactose, and their formation and degradation have been shown to be dependent upon lactose conversion. Both enzymes accumulate beta(1-->6)-linked glycosides, particularly allolactose, at a late stage of reaction. Because a high oligosaccharide concentration prevails until about 80% lactose conversion, thermostable beta-glycosidases are efficient for oligosaccharide production from lactose. Therefore, they prove to be stable and versatile catalysts for lactose utilization. PMID:10861393

  20. Utility of tricalcium phosphate and osteogenic matrix cell sheet constructs for bone defect reconstruction

    PubMed Central

    Ueha, Tomoyuki; Akahane, Manabu; Shimizu, Takamasa; Uchihara, Yoshinobu; Morita, Yusuke; Nitta, Naoya; Kido, Akira; Inagaki, Yusuke; Kawate, Kenji; Tanaka, Yasuhito

    2015-01-01

    AIM: To determine the effects of transplanting osteogenic matrix cell sheets and beta-tricalcium phosphate (TCP) constructs on bone formation in bone defects. METHODS: Osteogenic matrix cell sheets were prepared from bone marrow stromal cells (BMSCs), and a porous TCP ceramic was used as a scaffold. Three experimental groups were prepared, comprised of TCP scaffolds (1) seeded with BMSCs; (2) wrapped with osteogenic matrix cell sheets; or (3) both. Constructs were implanted into a femoral defect model in rats and bone growth was evaluated by radiography, histology, biochemistry, and mechanical testing after 8 wk. RESULTS: In bone defects, constructs implanted with cell sheets showed callus formation with segmental or continuous bone formation at 8 wk, in contrast to TCP seeded with BMSCs, which resulted in bone non-union. Wrapping TCP constructs with osteogenic matrix cell sheets increased their osteogenic potential and resulting bone formation, compared with conventional bone tissue engineering TCP scaffolds seeded with BMSCs. The compressive stiffness (mean ± SD) values were 225.0 ± 95.7, 30.0 ± 11.5, and 26.3 ± 10.6 MPa for BMSC/TCP/Sheet constructs with continuous bone formation, BMSC/TCP/Sheet constructs with segmental bone formation, and BMSC/TCP constructs, respectively. The compressive stiffness of BMSC/TCP/Sheet constructs with continuous bone formation was significantly higher than those with segmental bone formation and BMSC/TCP constructs. CONCLUSION: This technique is an improvement over current methods, such as TCP substitution, and is useful for hard tissue reconstruction and inducing earlier bone union in defects. PMID:26131318

  1. Using ice-penetrating radars to date ice-rise formation and Late Holocene ice-sheet retreat in the Ronne Ice Shelf region, West Antarctica

    NASA Astrophysics Data System (ADS)

    Kingslake, Jonathan; Hindmarsh, Richard; King, Edward; Corr, Hugh

    2015-04-01

    The history of the West Antarctic Ice Sheet in the region currently occupied by the Ronne Ice Shelf is poorly known. This reflects a lack of accessible recently deglaciated surfaces, which prohibits conventional paleo glaciological techniques that can provide evidence of past ice-sheet extent and retreat, for example ocean coring or exposure-dating of geological material. We use a glaciological technique, Raymond Effect Dating, to constrain the retreat of the ice sheet through the Ronne Ice Shelf region. During two Antarctic field seasons, we used a pulse-echo ice-penetrating radar to image the base and internal stratigraphy of four ice rises - areas of grounded ice containing ice divides. Towing the radar with skidoos, we conducted over 2000 km of surveys on the Skytrain, Korff, Henry and Fowler Ice Rises and the ice shelf between them. We also used a step-frequency radar called pRES to measure the vertical ice flow in the vicinity of each ice divide. Isochronal ice layers imaged during the surveys deforming in a predictable way with ice flow, meaning that their shape contains information about past ice flow. Directly beneath ice divides the downward motion of the ice is impeded by an ice-dynamical phenomenon called the Raymond Effect. This causes layers beneath the divides to form 'Raymond Arches' that grow over time. We will present the data and simulate the growth of the Raymond Arches using our pRES-measured vertical ice velocities and date the onset of ice-divide flow at each ice rise by comparing the size of simulated arches to the arches imaged during our radar surveys. We consider the main sources of uncertainty associated with these ice-rise formation dates and discuss what they can tell us about the retreat of the West Antarctic Ice Sheet through this region during the last few thousand years.

  2. Quantitative analysis of co-oligomer formation by amyloid-beta peptide isoforms.

    PubMed

    Iljina, Marija; Garcia, Gonzalo A; Dear, Alexander J; Flint, Jennie; Narayan, Priyanka; Michaels, Thomas C T; Dobson, Christopher M; Frenkel, Daan; Knowles, Tuomas P J; Klenerman, David

    2016-01-01

    Multiple isoforms of aggregation-prone proteins are present under physiological conditions and have the propensity to assemble into co-oligomers with different properties from self-oligomers, but this process has not been quantitatively studied to date. We have investigated the amyloid-β (Aβ) peptide, associated with Alzheimer's disease, and the aggregation of its two major isoforms, Aβ40 and Aβ42, using a statistical mechanical modelling approach in combination with in vitro single-molecule fluorescence measurements. We find that at low concentrations of Aβ, corresponding to its physiological abundance, there is little free energy penalty in forming co-oligomers, suggesting that the formation of both self-oligomers and co-oligomers is possible under these conditions. Our model is used to predict the oligomer concentration and size at physiological concentrations of Aβ and suggests the mechanisms by which the ratio of Aβ42 to Aβ40 can affect cell toxicity. An increased ratio of Aβ42 to Aβ40 raises the fraction of oligomers containing Aβ42, which can increase the hydrophobicity of the oligomers and thus promote deleterious binding to the cell membrane and increase neuronal damage. Our results suggest that co-oligomers are a common form of aggregate when Aβ isoforms are present in solution and may potentially play a significant role in Alzheimer's disease. PMID:27346247

  3. Quantitative analysis of co-oligomer formation by amyloid-beta peptide isoforms

    PubMed Central

    Iljina, Marija; Garcia, Gonzalo A.; Dear, Alexander J.; Flint, Jennie; Narayan, Priyanka; Michaels, Thomas C. T.; Dobson, Christopher M.; Frenkel, Daan; Knowles, Tuomas P. J.; Klenerman, David

    2016-01-01

    Multiple isoforms of aggregation-prone proteins are present under physiological conditions and have the propensity to assemble into co-oligomers with different properties from self-oligomers, but this process has not been quantitatively studied to date. We have investigated the amyloid-β (Aβ) peptide, associated with Alzheimer’s disease, and the aggregation of its two major isoforms, Aβ40 and Aβ42, using a statistical mechanical modelling approach in combination with in vitro single-molecule fluorescence measurements. We find that at low concentrations of Aβ, corresponding to its physiological abundance, there is little free energy penalty in forming co-oligomers, suggesting that the formation of both self-oligomers and co-oligomers is possible under these conditions. Our model is used to predict the oligomer concentration and size at physiological concentrations of Aβ and suggests the mechanisms by which the ratio of Aβ42 to Aβ40 can affect cell toxicity. An increased ratio of Aβ42 to Aβ40 raises the fraction of oligomers containing Aβ42, which can increase the hydrophobicity of the oligomers and thus promote deleterious binding to the cell membrane and increase neuronal damage. Our results suggest that co-oligomers are a common form of aggregate when Aβ isoforms are present in solution and may potentially play a significant role in Alzheimer’s disease. PMID:27346247

  4. Quantitative analysis of co-oligomer formation by amyloid-beta peptide isoforms

    NASA Astrophysics Data System (ADS)

    Iljina, Marija; Garcia, Gonzalo A.; Dear, Alexander J.; Flint, Jennie; Narayan, Priyanka; Michaels, Thomas C. T.; Dobson, Christopher M.; Frenkel, Daan; Knowles, Tuomas P. J.; Klenerman, David

    2016-06-01

    Multiple isoforms of aggregation-prone proteins are present under physiological conditions and have the propensity to assemble into co-oligomers with different properties from self-oligomers, but this process has not been quantitatively studied to date. We have investigated the amyloid-β (Aβ) peptide, associated with Alzheimer’s disease, and the aggregation of its two major isoforms, Aβ40 and Aβ42, using a statistical mechanical modelling approach in combination with in vitro single-molecule fluorescence measurements. We find that at low concentrations of Aβ, corresponding to its physiological abundance, there is little free energy penalty in forming co-oligomers, suggesting that the formation of both self-oligomers and co-oligomers is possible under these conditions. Our model is used to predict the oligomer concentration and size at physiological concentrations of Aβ and suggests the mechanisms by which the ratio of Aβ42 to Aβ40 can affect cell toxicity. An increased ratio of Aβ42 to Aβ40 raises the fraction of oligomers containing Aβ42, which can increase the hydrophobicity of the oligomers and thus promote deleterious binding to the cell membrane and increase neuronal damage. Our results suggest that co-oligomers are a common form of aggregate when Aβ isoforms are present in solution and may potentially play a significant role in Alzheimer’s disease.

  5. The human DEK oncogene stimulates beta catenin signaling, invasion and mammosphere formation in breast cancer

    PubMed Central

    Privette Vinnedge, Lisa M.; McClaine, Rebecca; Wagh, Purnima K.; Wikenheiser-Brokamp, Kathryn A.; Waltz, Susan E.; Wells, Susanne I.

    2011-01-01

    Breast cancer is a major cause of cancer-related deaths in American women; therefore, the identification of novel breast-cancer related molecules for the discovery of new markers and drug targets remains essential. The human DEK gene, which encodes a chromatin-binding protein and DNA topology regulator, is up-regulated in many types of cancer. DEK has been implicated as an oncogene in breast cancer based on mRNA expression studies, but its functional significance in breast cancer growth and progression has not yet been tested directly. We demonstrate that DEK is highly expressed in breast cancer cells compared to normal tissue, and functionally important for cellular growth, invasion and mammosphere formation. DEK over-expression in non-tumorigenic MCF10A cells resulted in increased growth and motility with a concomitant down-regulation of E-cadherin. Conversely, DEK knockdown in MCF7 and MDA-MB-468 breast cancer cells resulted in decreased growth and motility with up-regulation of E-cadherin. The use of DEK-proficient and -deficient breast cancer cells in orthotopic xenografts provided further in vivo evidence that DEK contributes to tumor growth. Activation of the β-catenin signaling pathway is important for normal and cancer stem cell character, growth and metastasis. We show that DEK expression stimulated and DEK knockdown repressed β-catenin nuclear translocation and activity. Importantly, the expression of constitutively active β-catenin rescued breast cancer invasion defects of DEK knockdown cells. Together, our data indicate that DEK expression stimulates the growth, stem cell character, and motility of breast cancer cells, and that DEK-dependent cellular invasion occurs at least in part via β-catenin activation. PMID:21317931

  6. Removal of the N-terminal hexapeptide from human beta2-microglobulin facilitates protein aggregation and fibril formation.

    PubMed Central

    Esposito, G.; Michelutti, R.; Verdone, G.; Viglino, P.; Hernández, H.; Robinson, C. V.; Amoresano, A.; Dal Piaz, F.; Monti, M.; Pucci, P.; Mangione, P.; Stoppini, M.; Merlini, G.; Ferri, G.; Bellotti, V.

    2000-01-01

    The solution structure and stability of N-terminally truncated beta2-microglobulin (deltaN6beta2-m), the major modification in ex vivo fibrils, have been investigated by a variety of biophysical techniques. The results show that deltaN6beta2-m has a free energy of stabilization that is reduced by 2.5 kcal/mol compared to the intact protein. Hydrogen exchange of a mixture of the truncated and full-length proteins at microM concentrations at pH 6.5 monitored by electrospray mass spectrometry reveals that deltaN6beta2-m is significantly less protected than its wild-type counterpart. Analysis of deltaN6beta2-m by NMR shows that this loss of protection occurs in beta strands I, III, and part of II. At mM concentration gel filtration analysis shows that deltaN6beta2-m forms a series of oligomers, including trimers and tetramers, and NMR analysis indicates that strand V is involved in intermolecular interactions that stabilize this association. The truncated species of beta2-microglobulin was found to have a higher tendency to self-associate than the intact molecule, and unlike wild-type protein, is able to form amyloid fibrils at physiological pH. Limited proteolysis experiments and analysis by mass spectrometry support the conformational modifications identified by NMR and suggest that deltaN6beta2-m could be a key intermediate of a proteolytic pathway of beta2-microglobulin. Overall, the data suggest that removal of the six residues from the N-terminus of beta2-microglobulin has a major effect on the stability of the overall fold. Part of the tertiary structure is preserved substantially by the disulfide bridge between Cys25 and Cys80, but the pairing between beta-strands far removed from this constrain is greatly perturbed. PMID:10850793

  7. Formation of. beta. ,. gamma. -methylene-7,8-dihydroneopterin 3'-triphosphate from. beta. ,. gamma. -methyleneguanosine 5'-triphosphate by GTP cyclohydrolase I of Escherichia coli

    SciTech Connect

    Ferre, J.; Jacobson, K.B.

    1984-01-01

    GTP cyclohydrolase I of Escherichia coli converts (..beta..,..gamma..-methylene)GTP to a fluorescent product that is characterized as (..beta..,..gamma..-methylene)dihydroneopterin triphosphate. Interaction between the GTP analog and the enzyme gave a K/sub i/ of 3.0 ..mu..M, which may be compared to the K/sub m/ of 0.1 ..mu..M for GTP. This new analog of dihydroneopterin triphosphate may, in turn, be converted to the same greenish-yellow pteridines (compounds X, X1, and X2) that are obtained from dihydroneopterin triphosphate. Because of its stability to phosphatase action, this analog may be useful for studies in pteridine metabolism. 14 references, 5 figures.

  8. Soluble penicillin-binding protein 2a: beta-lactam binding and inhibition by non-beta-lactams using a 96-well format.

    PubMed

    Toney, J H; Hammond, G G; Leiting, B; Pryor, K D; Wu, J K; Cuca, G C; Pompliano, D L

    1998-01-01

    High level methicillin resistance in Staphylococcus aureus is dependent upon the acquisition of the mecA gene encoding penicillin-binding protein 2a (PBP2a). PBP2a is a member of a family of peptidoglycan biosynthetic enzymes involved in assembly of the cell wall in bacteria and is poorly inactivated by beta-lactam antibiotics. We describe a 96-well-filter binding assay using recombinant, soluble PBP2a which allows for kinetic measurement of penicillin binding. The deacylation rate constant for the PBP2a-penicillin G covalent complex was found to be 5.7 +/- 1.0 x 10(-5) s-1 at 30 degrees C (half-life of approximately 200 min). For the PBP2a acylation reaction, the value of K(m) (penicillin G) = 0.5 +/- 0.1 mM and kcat = 1 x 10(-3) s-1, which yields a second-order rate constant (kcat/K(m)) for inactivation of 2.0 M-1 s-1. Using this assay, several non-beta-lactam inhibitors including Cibacron blue have been found which exhibit IC50 values between 10 and 30 microM. The binding affinities of several carbapenems and beta-lactams correlated well between the filter binding assay described in this report and an electrophoretic assay for PBP2a using membranes prepared form methicillin-resistant S. aureus. PMID:9448849

  9. AmrZ Beta-Sheet Residues Are Essential for DNA Binding and Transcriptional Control of Pseudomonas aeruginosa Virulence Genes ▿ †

    PubMed Central

    Waligora, Elizabeth A.; Ramsey, Deborah M.; Pryor, Edward E.; Lu, Haiping; Hollis, Thomas; Sloan, Gina P.; Deora, Rajendar; Wozniak, Daniel J.

    2010-01-01

    AmrZ is a putative ribbon-helix-helix (RHH) transcriptional regulator. RHH proteins utilize residues within the β-sheet for DNA binding, while the α-helices promote oligomerization. AmrZ is of interest due to its dual roles as a transcriptional activator and as a repressor, regulating genes encoding virulence factors associated with both chronic and acute Pseudomonas aeruginosa infection. In this study, cross-linking revealed that AmrZ forms oligomers in solution but that the amino terminus, containing an unordered region and a β-sheet, were not required for oligomerization. The first 12 unordered residues (extended amino terminus) contributed minimally to DNA binding. Mutagenesis of the AmrZ β-sheet demonstrated that residues 18, 20, and 22 were essential for DNA binding at both activation and repressor sites, suggesting that AmrZ utilizes a similar mechanism for binding to these sites. Mice infected with amrZ mutants exhibited reduced bacterial burden, morbidity, and mortality. Direct in vivo competition assays showed a 5-fold competitive advantage for the wild type over an isogenic amrZ mutant. Finally, the reduced infection phenotype of the amrZ-null strain was similar to that of a strain expressing a DNA-binding-deficient AmrZ variant, indicating that DNA binding and transcriptional regulation by AmrZ is responsible for the in vivo virulence defect. These recent infection data, along with previously identified AmrZ-regulated virulence factors, suggest the necessity of AmrZ transcriptional regulation for optimal virulence during acute infection. PMID:20709902

  10. [Beta]-Adrenergic Receptors in the Insular Cortex are Differentially Involved in Aversive vs. Incidental Context Memory Formation

    ERIC Educational Resources Information Center

    Miranda, Maria Isabel; Sabath, Elizabeth; Nunez-Jaramillo, Luis; Puron-Sierra, Liliana

    2011-01-01

    The goal of this research was to determine the effects of [beta]-adrenergic antagonism in the IC before or after inhibitory avoidance (IA) training or context pre-exposure in a latent inhibition protocol. Pretraining intra-IC infusion of the [beta]-adrenergic antagonist propranolol disrupted subsequent IA retention and impaired latent inhibition…

  11. Design of stable β-sheet-based cyclic peptide assemblies assisted by metal coordination: selective homo- and heterodimer formation.

    PubMed

    Panciera, Michele; Amorín, Manuel; Castedo, Luis; Granja, Juan R

    2013-04-01

    Metal-directed supramolecular construction represents one of the most powerful tools to prepare a large variety of structures and functions. The ability of metals to organize different numbers and types of ligands with a variety of geometries (linear, trigonal, octahedral, etc.) expands the supramolecular synthetic architecture. We describe here the precise construction of homo- and heterodimeric cyclic peptide entities through coordination of a metal (Pd, Au) and to β-sheet-type hydrogen-bonding interactions. The selective coordination properties of the appropriate metal allow control over the cross-strand interaction between the two-peptide strands. PMID:23423964

  12. Double Mantle Plume Upwelling—A Possible Formation Mechanism of Beta Plateau and Devana Chasma,Venus

    NASA Astrophysics Data System (ADS)

    Ding, N.

    2009-12-01

    Ning Ding,Zuoxun Zeng,China University of Geosciences,Wuhan,430074,China NingDing.eagle@gmail.com Introduction:Venus represents a‘one plate planet’[1],and the uplift,fractures and volcanism in Beta Regio on Venus are considered to be formed by lithosphere uplift driven by a hot plume[2]. Based on the double peaking saddle landform,we suggest the tectonic pattern of double mantle plume upwelling to interpret the formation mechanism of Beta Plateau and Devana Chasma.We take a physical modeling to validate this possibility. Model:There is no ductile shear in Venus[3],so we use quartz sands to simulate the crust of Venus.We use two wood stickes 1.5cm in diameter rising from the rubber canvas slowly and straight till about half of the model,then falling down slowly and straight.The base is a hard rubber plate,in the center of which,there are two holes 3cm in diameter,and the distance between them is 5cm.The holes are covered by rubber canvas.We use the quartz sands in colours of white, red and black with particle size of 70 mess as the model materials. Result:Fig.1:At the beginning of the wood stickes upwelling,only fine radial cracks are formed above the upwelling from central to outside.With the upwelling continue,surface energy of the fine radial cracks increase and make the cracks unstable,finally,the fine radial cracks connect each other and form a fracture zone.And then the two mantle plume downwelling,the fracture zone is developed to form a chasma at the end. Fig.2:The four profiles all form reverse faults outside and normal faults inside.But the difference is the faults in the middle of the chasma goes deeper than others.It is the pattern of Beta Plateau where the tectonic rising is cut by Devana Chasma zone in the topographic features. Fig.3:From the tow fig., we can see two points similar:a.the elevation is high and distribution area is large around the area of two upwelling and it is high around the area of chasma,but the distribution area is small

  13. Computational study on the aminolysis of beta-hydroxy-alpha,beta-unsaturated ester via the favorable path including the formation of alpha-oxo ketene intermediate.

    PubMed

    Jin, Lu; Xue, Ying; Zhang, Hui; Kim, Chan Kyung; Xie, Dai Qian; Yan, Guo Sen

    2008-05-15

    The possible mechanisms of the aminolysis of N-methyl-3-(methoxycarbonyl)-4-hydroxy-2-pyridone (beta-hydroxy-alpha,beta-unsaturated ester) with dimethylamine are investigated at the hybrid density functional theory B3LYP/6-31G(d,p) level in the gas phase. Single-point computations at the B3LYP/6-311++G(d,p) and the Becke88-Becke95 1-parameter model BB1K/6-311++G(d,p) levels are performed for more precise energy predictions. Solvent effects are also assessed by single-point calculations at the integral equation formalism polarized continuum model IEFPCM-B3LYP/6-311++G(d,p) and IEFPCM-BB1K/6-311++G(d,p) levels on the gas-phase optimized geometries. Three possible pathways, the concerted pathway (path A), the stepwise pathway involving tetrahedral intermediates (path B), and the stepwise pathway via alpha-oxo ketene intermediate due to the participation of beta-hydroxy (path C), are taken into account for the title reaction. Moreover, path C includes two sequential processes. The first process is to generate alpha-oxo ketene intermediate via the decomposition of N-methyl-3-(methoxycarbonyl)-4-hydroxy-2-pyridone; the second process is the addition of dimethylamine to alpha-oxo ketene intermediate. Our results indicate that path C is more favorable than paths A and B both in the gas phase and in solvent (heptane). In path C, the first process is the rate-determining step, and the second process is revealed to be a [4+2] pseudopericyclic reaction without the energy barrier. Being independent of the concentration of amine, the first process obeys the first-order rate law. PMID:18402429

  14. Germinal center formation, immunoglobulin class switching, and autoantibody production driven by "non alpha/beta" T cells

    PubMed Central

    1996-01-01

    The production of class-switched antibodies, particularly immunoglobulin (Ig) G1 and IgE, occurs efficiently in T cell receptor (TCR) alpha-/- mice that are congenitally devoid of alpha/beta T cells. This finding runs counter to a wealth of data indicating that IgG1 and IgE synthesis are largely dependent on the collaboration between B and alpha/beta T cells. Furthermore, many of the antibodies synthesized in TCR alpha-/- mice are reactive to a similar spectrum of self-antigens as that targeted by autoantibodies characterizing human systemic lupus erythematosus (SLE). SLE, too, is most commonly regarded as an alpha/beta T cell-mediated condition. To distinguish whether the development of autoantibodies in TCR alpha-/- mice is due to an intrinsic de-regulation of B cells, or to a heretofore poorly characterized collaboration between B and "non-alpha/beta T" cells, the phenotype has been reconstituted by transfer of various populations of B and non-alpha/beta T cells including cloned gamma/delta T cells derived from TCR alpha-/- mice, to severe combined immunodeficient (SCID) mice. The results establish that the reproducible production of IgG1 (including autoantibodies) is a product of non-alpha/beta T cell help that can be provided by gamma/delta T cells. This type of B-T collaboration sustains the production of germinal centers, lymphoid follicles that ordinarily are anatomical signatures of alpha/beta T-B cell collaboration. Thus, non-alpha/beta T cell help may drive Ig synthesis and autoreactivity under various circumstances, especially in cases of alpha/beta T cell immunodeficiency. PMID:8642336

  15. Polymer bilayer formation due to specific interactions between beta-cyclodextrin and adamantane: a surface force study.

    PubMed

    Blomberg, Eva; Kumpulainen, Atte; David, Christelle; Amiel, Catherine

    2004-11-23

    The purposes of this study are to utilize the interactions between an adamantane end-capped poly(ethylene oxide) (PEO) and a cationic polymer of beta-cyclodextrin to build polymer bilayers on negatively charged surfaces, and to investigate the interactions between such layers. The association of this system in solution has been studied by rheology, light scattering, and fluorescence measurements. It was found that the adamantane-terminated PEO (PEO-Ad) mixed with the beta-cyclodextrin polymer gives complexes where the interpolymer links are formed by specific inclusion of the adamantane groups in the beta-cyclodextrin cavities. This results in a higher viscosity of the solution and growth of intermolecular clusters. The interactions between surfaces coated with a cationized beta-cyclodextrin polymer across a water solution containing PEO-Ad polymers were studied by employing the interferometric surface force apparatus (SFA). In the first step, the interaction between mica surfaces coated with the cationized beta-cyclodextrin polymer in pure water was investigated. It was found that the beta-cyclodextrin polymer adsorbs onto mica and almost neutralizes the surface charge. The adsorbed layers of the beta-cyclodextrin polymer are rather compact, with a layer thickness of about 60 A (30 A per surface). Upon separation, a very weak attractive force is observed. The beta-cyclodextrin solution was then diluted by pure water by a factor of 3000 and a PEO-Ad polymer was introduced into the solution. Two different architectures of the PEO-Ad polymer were investigated: a four-arm structure and a linear structure. After the adsorption of the PEO polymer onto the beta-cyclodextrin layer reached equilibrium, the forces were measured again. It was found that the weak repulsive long-range force had disappeared and an attractive force caused the surfaces to jump into contact, and that the compressed layer thickness had increased. The attractive force is interpreted as being due to

  16. Formation and growth of oligomers: a Monte Carlo study of an amyloid tau fragment.

    PubMed

    Li, Da-Wei; Mohanty, Sandipan; Irbäck, Anders; Huo, Shuanghong

    2008-12-01

    Small oligomers formed early in the process of amyloid fibril formation may be the major toxic species in Alzheimer's disease. We investigate the early stages of amyloid aggregation for the tau fragment AcPHF6 (Ac-VQIVYK-NH2) using an implicit solvent all-atom model and extensive Monte Carlo simulations of 12, 24, and 36 chains. A variety of small metastable aggregates form and dissolve until an aggregate of a critical size and conformation arises. However, the stable oligomers, which are beta-sheet-rich and feature many hydrophobic contacts, are not always growth-ready. The simulations indicate instead that these supercritical oligomers spend a lengthy period in equilibrium in which considerable reorganization takes place accompanied by exchange of chains with the solution. Growth competence of the stable oligomers correlates with the alignment of the strands in the beta-sheets. The larger aggregates seen in our simulations are all composed of two twisted beta-sheets, packed against each other with hydrophobic side chains at the sheet-sheet interface. These beta-sandwiches show similarities with the proposed steric zipper structure for PHF6 fibrils but have a mixed parallel/antiparallel beta-strand organization as opposed to the parallel organization found in experiments on fibrils. Interestingly, we find that the fraction of parallel beta-sheet structure increases with aggregate size. We speculate that the reorganization of the beta-sheets into parallel ones is an important rate-limiting step in the formation of PHF6 fibrils.

  17. Inhibitory effect of Bifidobacterium longum cultures on the azoxymethane-induced aberrant crypt foci formation and fecal bacterial beta-glucuronidase.

    PubMed

    Kulkarni, N; Reddy, B S

    1994-12-01

    Epidemiologic and experimental studies suggest that consumption of fermented milk products and lactic bacterial cultures that are used to ferment the dairy products, decrease the incidence of certain types of cancer. The present study was designed to determine the effect of lyophilized cultures of Bifidobacterium longum (B. longum), a lactic bacteria, on the azoxymethane (AOM)-induced preneoplastic lesions such as aberrant crypt foci (ACF) formation in the colon and on fecal bacterial beta-glucuronidase activity in male F344 rats. At 5 weeks of age, groups of animals were fed the AIN-76A (control) and the experimental diets containing 1.5% and 3% lyophilized cultures of B. longum. At 10 weeks of age, all animals received sc injection of AOM dissolved in normal saline at a dose rate of 20 mg/kg body wt, once weekly for 2 weeks. The animals were necropsied 6 weeks after the last AOM injection, and the ACF were visualized under light microscopy in the formalin-fixed, unsectioned methylene blue-stained colons where they were distinguished by their increased size, more prominent epithelial cells, and pericryptal space. The cecal contents were analyzed for bacterial beta-glucuronidase activity. The feeding of lyophilized cultures of B. longum significantly inhibited the ACF formation (53%) and the crypt multiplicity in the colon. A significant decrease in the fecal bacterial beta-glucuronidase was also observed in the animals fed the diets containing Bifidobacterium supplements as compared with control diet. These results demonstrate that B. longum in diet influences the metabolic activity of certain types of intestinal microflora that are involved in the production of beta-glucuronidase. Furthermore, the findings also suggest that B. longum supplements inhibit ACF formation, an early preneoplastic marker of malignant potential in the process of colon carcinogenesis.

  18. Stability of single sheet GNNQQNY aggregates analyzed by replica exchange molecular dynamics: Antiparallel versus parallel association

    SciTech Connect

    Vitagliano, Luigi; Esposito, Luciana; Pedone, Carlo; De Simone, Alfonso

    2008-12-26

    Protein and peptide aggregation into amyloid plaques is associated with a large variety of neurodegenerative diseases. The definition of the molecular bases of these pathologies is hampered by the transient nature of pre-fibrillar small-oligomers that are considered the toxic species. The ability of the peptide GNNQQNY to form amyloid-like structures makes it a good model to investigate the complex processes involved into amyloid fiber formation. By employing full atomistic replica exchange molecular dynamics simulations, we constructed the free energy surface of small assemblies of GNNQQNY to gain novel insights into the fiber formation process. The calculations suggest that the peptide exhibits a remarkable tendency to form both parallel and antiparallel {beta}-sheets. The data show that GNNQQNY preference for parallel or antiparallel {beta}-sheets is governed by a subtle balance of factors including assemblies' size, sidechain-sidechain interactions and pH. The samplings analysis provides a rationale to the observed trends.

  19. Splicing and 3' end formation in the definition of nonsense-mediated decay-competent human beta-globin mRNPs.

    PubMed

    Neu-Yilik, G; Gehring, N H; Thermann, R; Frede, U; Hentze, M W; Kulozik, A E

    2001-02-01

    Premature translation termination codons are common causes of genetic disorders. mRNAs with such mutations are degraded by a surveillance mechanism termed nonsense-mediated decay (NMD), which represents a phylogenetically widely conserved post-transcriptional mechanism for the quality control of gene expression. How NMD-competent mRNPs are formed and specified remains a central question. Here, we have used human beta-globin mRNA as a model system to address the role of splicing and polyadenylation for human NMD. We show that (i) splicing is an indispensable component of the human beta-globin NMD pathway, which cannot be compensated for by exonic beta-globin 'failsafe' sequences; (ii) the spatial requirements of human beta-globin NMD, as signified by the maximal distance of the nonsense mutation to the final exon-exon junction, are less constrained than in yeast; and (iii) non-polyadenylated mRNAs with a histone 3' end are NMD competent. Thus, the formation of NMD-competent mRNP particles critically depends on splicing but does not require the presence of a poly(A) tail.

  20. Till formation under a soft-bedded palaeo-ice stream of the Scandinavian Ice Sheet, constrained using qualitative and quantitative microstructural analyses

    NASA Astrophysics Data System (ADS)

    Narloch, Włodzimierz; Piotrowski, Jan A.; Wysota, Wojciech; Tylmann, Karol

    2015-08-01

    This study combines micro- and macroscale studies, laboratory experiments and quantitative analyses to decipher processes of till formation under a palaeo-ice stream and the nature of subglacial sediment deformation. Till micromorphology (grain lineations, grain stacks, turbate structures, crushed grains, intraclasts and domains), grain-size and till fabric data are used to investigate a basal till generated by the Vistula Ice Stream of the Scandinavian Ice Sheet during the last glaciation in north-central Poland. A comparison of microstructures from the in situ basal till and laboratory-sheared till experiments show statistical relationships between the number of grain lineations and grain stacks; and between the number of grain lineations and turbate structures. Microstructures in the in situ till document both brittle and ductile styles of deformation, possibly due to fluctuating basal water pressures beneath the ice stream. No systematic vertical and lateral trends are detected in the parameters investigated in the in situ till, which suggests a subglacial mosaic of relatively stable and unstable areas. This situation can be explained by an unscaled space-transgressive model of subglacial till formation whereby at any given point in time different processes operated in different places under the ice sheet, possibly related to the distance from the ice margin and water pressure at the ice-bed interface. A new quantitative measure reflecting the relationship between the number of grain lineations and grain stacks may be helpful in discriminating between pervasive and non-pervasive deformation and constraining the degree of stress heterogeneity within a deformed bed. Independent strain magnitude estimations revealed by a quantitative analysis of micro- and macro-particle data show low cumulative strain in the ice-stream till in the order of 10-102.

  1. Calcium ion-induced formation of β-sheet/-turn structure leading to alteration of osteogenic activity of bone morphogenetic protein-2.

    PubMed

    Zhang, Wenjing; He, Hongyan; Tian, Yu; Gan, Qi; Zhang, Jing; Yuan, Yuan; Liu, Changsheng

    2015-07-27

    Preserving bioactivity of bone morphogenetic protein 2 (BMP-2) still remains a challenge in protein-based therapy. It is not known how Ca(2+) released from extracellular matrix or existing in physiological environment influences bioactivity in situ till now. Here, effects of extracellular Ca(2+) on conformation and osteogenic bioactivity of recombinant human BMP-2 (rhBMP-2) were investigated systematically. In vitro results indicated that Ca(2+) could bind rhBMP-2 rapidly and had no obvious effect on cell behaviors. Low concentration of Ca(2+) (0.18 mM) enhanced rhBMP-2-induced osteogenic differentiation, while high Ca(2+) concentration (>1.80 mM) exerted negative effect. In vivo ectopic bone formation exhibited similar trend. Further studies by circular dichroism spectroscopy, fluorescence spectroscopy, together with cell culture experiments revealed at low concentration, weak interaction of Ca(2+) and rhBMP(-)2 slightly increased β-sheet/-turn content and facilitated recognition of BMP-2 and BMPRIA. But, high Ca(2+) concentration (>1.8 mM) induced formation of Ca-rhBMP-2 complex and markedly increased content of β-sheet/-turn, which led to inhibition binding of rhBMP-2 and BMPRIA and thus suppression of downstream Smad1/5/8, ERK1/2 and p38 mitogen-associated protein kinase signaling pathways. Our work suggests osteogenic bioactivity of BMP-2 can be adjusted via extracellular Ca(2+), which should provide guide and assist for development of BMP-2-based materials for bone regeneration.

  2. Fibril stability in solutions of twisted Format="TEX"/>-sheet peptides: a new kind of micellization in chiral systems

    NASA Astrophysics Data System (ADS)

    Nyrkova, I. A.; Semenov, A. N.; Aggeli, A.; Boden, N.

    2000-10-01

    The problem of fibril (fibre) formation in chiral systems is explored theoretically being supported by experiments on synthetic de novo 11-mer peptide forming self-assembled -sheet tapes. Experimental data unambiguously indicate that the tapes form fibrils of nearly monodisperse thickness ca. 8-10 nm. Fibril formation and stabilisation are attributed to inter-tape face-to-face attraction and their intrinsic twist, correspondingly. The proposed theory is capable of predicting the fibril aggregation number and its equilibrium twist in terms of molecular parameters of the primary tapes. The suggested novel mechanism of twist stabilisation of finite aggregates (fibrils) is different to the well-known stabilisation of micelles in amphiphilic systems, and it is likely to explain the formation and stability of fibrils in a wide variety of systems including proteinaceous amyloid fibres, sickle-cell hemoglobin fibres responsible for HbS anemia, corkscrew threads found in chromonics in the presence of chiral additives and native cellulose microfibrillar crystallites. The theory also makes it possible to extract the basic molecular parameters of primary tapes (inter-tape attraction energy, helical twist step, elastic moduli) from the experimental data.

  3. Formation of {beta}-nickel hydroxide plate-like structures under mild conditions and their optical properties

    SciTech Connect

    Moura, A.P. de; Lima, R.C.; Paris, E.C.; Li, M.S.; Varela, J.A.; Longo, E.

    2011-10-15

    Nanostructural {beta}-nickel hydroxide ({beta}-Ni(OH){sub 2}) plates were prepared using the microwave-hydrothermal (MH) method at a low temperature and short reaction times. An ammonia solution was employed as the coordinating agent, which reacts with [Ni(H{sub 2}O){sub 6}]{sup 2+} to control the growth of {beta}-Ni(OH){sub 2} nuclei. A trigonal {beta}-Ni(OH){sub 2} single phase was observed by X-ray diffraction (XRD) analyses, and the crystal cell was constructed with structural parameters and atomic coordinates obtained from Rietveld refinement. Field emission scanning electron microscopy (FE-SEM) images revealed that the samples consisted of hexagonal-shaped nanoplates with a different particle size distribution. Broad absorption bands assigned as transitions of Ni{sup 2+} in oxygen octahedral sites were revealed by UV-vis spectra. Photoluminescence (PL) properties observed with a maximum peak centered in the blue-green region were attributed to different defects, which were produced during the nucleation process. We present a growth process scheme of the {beta}-Ni(OH){sub 2} nanoplates. - Graphical abstract: Nanostructural {beta}-Ni(OH){sub 2} crystalline powders were prepared by rapid microwave-hydrothermal method for 1, 8 and 32 min. The hexagonal-shaped nanoplates obtained presented PL emission in the blue-green region and each decomposed component represents a different type of electronic transition, which can be linked to the structural arrangement or surface defects. Highlights: > Ammonia solution to control the growth of {beta}-Ni(OH){sub 2} nuclei. > Regular plates-shape related to crystallization-dissolution-recrystallization. > The surface states and lattice defects generated in growth mechanism of crystals. > Different defects produced in the growth process responsible by photoluminescence. > Each component of photoluminescence curve linked to structural arrangement or surface defects.

  4. The Influence of Welding Parameters on the Nugget Formation of Resistance Spot Welding of Inconel 625 Sheets

    NASA Astrophysics Data System (ADS)

    Rezaei Ashtiani, Hamid Reza; Zarandooz, Roozbeh

    2015-09-01

    A 2D axisymmetric electro-thermo-mechanical finite element (FE) model is developed to investigate the effect of current intensity, welding time, and electrode tip diameter on temperature distributions and nugget size in resistance spot welding (RSW) process of Inconel 625 superalloy sheets using ABAQUS commercial software package. The coupled electro-thermal analysis and uncoupled thermal-mechanical analysis are used for modeling process. In order to improve accuracy of simulation, material properties including physical, thermal, and mechanical properties have been considered to be temperature dependent. The thickness and diameter of computed weld nuggets are compared with experimental results and good agreement is observed. So, FE model developed in this paper provides prediction of quality and shape of the weld nuggets and temperature distributions with variation of each process parameter, suitably. Utilizing this FE model assists in adjusting RSW parameters, so that expensive experimental process can be avoided. The results show that increasing welding time and current intensity lead to an increase in the nugget size and electrode indentation, whereas increasing electrode tip diameter decreases nugget size and electrode indentation.

  5. Late Noachian and early Hesperian ridge systems in the south circumpolar Dorsa Argentea Formation, Mars: Evidence for two stages of melting of an extensive late Noachian ice sheet

    NASA Astrophysics Data System (ADS)

    Kress, Ailish M.; Head, James W.

    2015-05-01

    The Dorsa Argentea Formation (DAF), extending from 270°-100° E and 70°-90° S, is a huge circumpolar deposit surrounding and underlying the Late Amazonian South Polar Layered Deposits (SPLD) of Mars. Currently mapped as Early-Late Hesperian in age, the Dorsa Argentea Formation has been interpreted as volatile-rich, possibly representing the remnants of an ancient polar ice cap. Uncertain are its age (due to the possibility of poor crater retention in ice-related deposits), its mode of origin, the origin of the distinctive sinuous ridges and cavi that characterize the unit, and its significance in the climate history of Mars. In order to assess the age of activity associated with the DAF, we examined the ridge populations within the Dorsa Argentea Formation, mapping and characterizing seven different ridge systems (composed of nearly 4,000 ridges covering a total area of ~300,000 km2, with a cumulative length of ridges of ~51,000 km) and performing crater counts on them using the method of buffered crater counting to determine crater retention ages of the ridge populations. We examined the major characteristics of the ridge systems and found that the majority of them were consistent with an origin as eskers, sediment-filled subglacial drainage channels. Ridge morphologies reflect both distributed and channelized esker systems, and evidence is also seen that some ridges form looping moraine-like termini distal to some distributed systems. The ridge populations fall into two age groups: ridge systems between 270° and 0° E date to the Early Hesperian, but to the east, the Promethei Planum and the Chasmata ridge systems date to the Late Noachian. Thus, these ages, and esker and moraine-like morphologies, support the interpretation that the DAF is a remnant ice sheet deposit, and that the esker systems represent evidence of significant melting and drainage of meltwater from portions of this ice sheet, thus indicating at least some regions and/or periods of wet

  6. Sensitivity enhanced (14)N/(14)N correlations to probe inter-beta-sheet interactions using fast magic angle spinning solid-state NMR in biological solids.

    PubMed

    Pandey, Manoj Kumar; Amoureux, Jean-Paul; Asakura, Tetsuo; Nishiyama, Yusuke

    2016-08-10

    observation of inter-β-sheet correlations. PMID:27477057

  7. Sensitivity enhanced (14)N/(14)N correlations to probe inter-beta-sheet interactions using fast magic angle spinning solid-state NMR in biological solids.

    PubMed

    Pandey, Manoj Kumar; Amoureux, Jean-Paul; Asakura, Tetsuo; Nishiyama, Yusuke

    2016-08-10

    observation of inter-β-sheet correlations.

  8. The region of formation of the ultraviolet high temperature resonance lines in the eclipsing binary Beta Persei (Algol)

    NASA Technical Reports Server (NTRS)

    Brandi, E.; Garcia, L. G.; Kondo, Y.; Sahade, J.

    1989-01-01

    A new series of IUE observations of Beta Persei has shown that the high temperature resonance lines of Si IV and C IV arise in a region that surrounds the brighter, early-type component of the system. The continuum spectrum corresponds to that of a B8V object, and the value of E(B-V) that yielded the best match between the two IUE regions was 0.06, the value quoted for Beta Per in Jamar et al.'s (1976) Catalog.

  9. Development of a novel composite material with carbon nanotubes assisted by self-assembled peptides designed in conjunction with β-sheet formation.

    PubMed

    Hashida, Yasuhiko; Umeyama, Tomokazu; Mihara, Junya; Imahori, Hiroshi; Tsujimoto, Masahiko; Isoda, Seiji; Takano, Mikio; Hashida, Mitsuru

    2012-09-01

    A novel composite material is developed with single-walled carbon nanotubes (SWCNTs) and artificially designed peptides, and its chemical and physicochemical characteristics are evaluated with an aim toward biomedical application. The peptides were designed to form a β-sheet structure that would be suitable for wrapping SWCNTs. The complex of SWCNTs and peptide (SWCNT-peptide) showed good dispersibility in aqueous media and was considerably stable even in the absence of an excess amount of peptide in the media. The formation of SWCNT-peptide was confirmed by its performance in water, atomic force microscopy and transmission electron microscopy observation, and molecular modeling. The possibility of introducing various functions to SWCNT-peptide was also demonstrated by several methods, such as introduction of special amino acids, chemical modification, and additional complex formation based on electrostatic interaction. These results suggest the potential of the SWCNT-peptide complex as a molecular platform on which a desirable structure and/or function can be constructed for biomedical and industrial application.

  10. FORMATION OF BETA-HYDROXYCARBONYLS FROM THE OH RADICAL-INITIATED REACTIONS OF SELECTED ALKENES (R825252)

    EPA Science Inventory

    beta2.gif" BORDER=0 ALIGN="middle">-Hydroxycarbonyls can be formed from the gas-phase
    reactions of alkenes with the OH radical, both in the presence
    and in the absence of NO. To date, because of analytical
    difficulties, few data have been r...

  11. On the biodegradation of beta-peptides.

    PubMed

    Schreiber, Jürg V; Frackenpohl, Jens; Moser, Frank; Fleischmann, Thomas; Kohler, Hans-Peter E; Seebach, Dieter

    2002-05-01

    A consortium of microorganisms was established that was able to grow with the beta-tripeptide H-beta-HVal-beta-HAla-beta-HLeu-OH, with the beta-dipeptide H-beta-HAla-beta-HLeu-OH, and with the beta-amino acids H-beta-HAla-OH, H-beta-HVal-OH, and H-beta-HLeu-OH as the sole carbon and energy sources. This growth was achieved after several incubation-transfer cycles with the beta-tripeptide as the substrate. During degradation of the beta-tripeptide H-beta-HVal-beta-HAla-beta-HLeu-OH, the temporary formation of a metabolite was observed. The metabolite was identified as the beta-dipeptide H-beta-HAla-beta-HLeu-OH by nuclear magnetic resonance spectroscopy and mass spectrometry. This result indicates that in the course of the degradation of the beta-tripeptide, the N-terminal beta-HVal residue was cleaved off by a not yet known mechanism. During the subsequent degradation of the beta-dipeptide, formation of additional metabolites could not be detected. The growth-yield coefficients Y(x/s) for growth on the beta-di- and beta-tripeptide both had a value of 0.45. When a 1:1 mixture of the beta-tripeptide and the corresponding alpha-tripeptide H-Val-Ala-Leu-OH was added to the enrichment culture, the alpha-peptide was completely utilized in six days and thereafter growth of the culture stopped. This result indicates that even in beta-peptide enrichment cultures, alpha-peptides are the preferred substrates. Our experiments clearly show for the first time that beta-peptides and beta-amino acids are amenable to biodegradation and that a microbial consortium was able to utilize these compounds as sole carbon and energy sources. Furthermore, the preparation of beta-amino acids, of derivatives thereof, and of beta-di- and beta-tripeptides is described.

  12. Shear flow promotes amyloid-{beta} fibrilization.

    PubMed

    Dunstan, Dave E; Hamilton-Brown, Paul; Asimakis, Peter; Ducker, William; Bertolini, Joseph

    2009-12-01

    The rate of formation of amyloid fibrils in an aqueous solution of amyloid-beta (Abeta) is greatly increased when the solution is sheared. When Abeta solution is stirred with a magnetic stirrer bar at 37 degrees C, a rapid increase in thioflavin T fluorescence is observed. Atomic Force Microscopy (AFM) images show the formation of aggregates, the growth of fibrils and the intertwining of the fibrils with time. Circular dichroism (CD) spectroscopy of samples taken after stirring shows a transition from random coil to alpha-helix to beta-sheet secondary structure over 20 h at 37 degrees C. The fluorescence, AFM and CD measurements are all consistent with the formation of amyloid fibrils. Quiescent, non-stirred solutions incubated at 37 degrees C showed no evidence of amyloid formation over a period of 3 days. Couette flow was found to accelerate the formation of amyloid fibrils demonstrating that the primary effect of stirring is not mixing but shearing. Only very small shear forces are applied to individual molecules in our experiments. Simple calculation suggests that the force is too small to support a hypothesis that shearing promotes partial unfolding of the protein as is observed. PMID:19850675

  13. TGF{beta}-mediated formation of pRb-E2F complexes in human myeloid leukemia cells

    SciTech Connect

    Hu Xiaotang

    2008-05-02

    TGF{beta} is well known for its inhibitory effect on cell cycle G1 checkpoint kinases. However, its role in the control of pRb-E2F complexes is not well established. TGF{beta} inhibits phosphorylation of pRb at several serine and threonine residues and regulates the association of E2F transcription factors with pRb family proteins. Recent studies found that predominantly E2F-4, p130, and histone deacetylase (HDAC) are found to bind to corresponding E2F-responsive promoters in G0/G1 phase. As cells progress through mid-G1, p130-E2F4 complex are replaced by p107-E2F4 followed by activators E2F1, 2, and 3. pRb was not detectable in the promoters containing the E2F-responsive site in cycling cells but was associated with E2F4-p130 complexes or E2F4-p107 complexes during G0/G1 phase. In human myeloid leukemia cell line, MV4-11, TGF{beta} upregulated pRb-E2F-4 and p130-E2F-4, and downregulated p107-E2F-4 complexes. However, pRB-E2F1 and pRb-E2F3 complexes were found in proliferating cells but not in TGF{beta} arrested G1 cells. In addition, electrophoretic gel mobility shift assay (EMSA) could not detect pRb-E2F DNA-binding activities either in S or G1 phase but exhibited the existence of p107-E2F4 in proliferating cells and p130-E2F4 complexes in TGF{beta}-arrested G1 cells, respectively. Our data suggest that p107 and p130, but not pRb, and the repressor E2F, but not activator E2Fs, play a critical role in regulating E2F-responsive gene expression in TGF{beta}-mediated cell cycle control in human myeloid leukemia cells.

  14. Structural studies of the N-terminal fragments of the WW domain: Insights into co-translational folding of a beta-sheet protein

    PubMed Central

    Hanazono, Yuya; Takeda, Kazuki; Miki, Kunio

    2016-01-01

    Nascent proteins fold co-translationally because the folding speed and folding pathways are limited by the rate of ribosome biosynthesis in the living cell. In addition, though full-length proteins can fold all their residues during the folding process, nascent proteins initially fold only with the N-terminal residues. However, the transient structure and the co-translational folding pathway are not well understood. Here we report the atomic structures of a series of N-terminal fragments of the WW domain with increasing amino acid length. Unexpectedly, the structures indicate that the intermediate-length fragments take helical conformations even though the full-length protein has no helical regions. The circular dichroism spectra and theoretical calculations also support the crystallographic results. This suggests that the short-range interactions are more decisive in the structure formation than the long-range interactions for short nascent proteins. In the course of the peptide extension, the helical structure change to the structure mediated by the long-range interactions at a particular polypeptide length. Our results will provide unique information for elucidating the nature of co-translational folding. PMID:27698466

  15. Overexpression of granulocyte-macrophage colony-stimulating factor induces pulmonary granulation tissue formation and fibrosis by induction of transforming growth factor-beta 1 and myofibroblast accumulation.

    PubMed Central

    Xing, Z.; Tremblay, G. M.; Sime, P. J.; Gauldie, J.

    1997-01-01

    We have previously reported that transfer to rat lung of the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene leads to high expression of GM-CSF between days 1 and 4 and granulation tissue formation followed by an irreversible fibrotic response starting from day 12 onward. In the current study, we investigated the underlying mechanisms. We found that GM-CSF overexpression did not enhance production of tumor necrosis factor-alpha in a significant manner at any time after GM-CSF gene transfer. However, the content of transforming growth factor-beta 1 in bronchoalveolar lavage fluid was markedly induced at day 4 and appeared to be maximal around day 7 and remained high at day 12. Macrophages purified from bronchoalveolar lavage fluid 7 days after GM-CSF gene transfer spontaneously released significant quantities of transforming growth factor-beta 1 protein in vitro. After peak transforming growth factor-beta 1 production was the emergence of alpha-smooth muscle actin-rich myofibroblasts. Accumulation of these cells was most prominent at day 12 within the granulation tissues and they were still present in fibrotic areas between days 12 and 24 and diminished markedly afterward. Thus, we provide the first in vivo evidence that tumor necrosis factor-alpha may be dissociated from participation in a fibrotic process in the lung and GM-CSF may play a more direct role in pulmonary fibrogenesis at least in part through its capability to induce transforming growth factor-beta 1 in macrophages and the subsequent emergence of myofibroblast phenotypes. This GM-CSF transgene lung model is useful for a stepwise dissection of both cellular and molecular events involved in pulmonary fibrosis. Images Figure 2 Figure 5 Figure 6 PMID:9006322

  16. Rationally designed peptoids modulate aggregation of amyloid-beta 40.

    PubMed

    Turner, J Phillip; Lutz-Rechtin, Tammy; Moore, Kelly A; Rogers, Lauren; Bhave, Omkar; Moss, Melissa A; Servoss, Shannon L

    2014-07-16

    Alzheimer's disease (AD) is the most common form of dementia and the sixth leading cause of death in the United States. Plaques composed of aggregated amyloid-beta protein (Aβ) accumulate between the neural cells in the brain and are associated with dementia and cellular death. Many strategies have been investigated to prevent Aβ self-assembly into disease-associated β-sheet amyloid aggregates; however, a promising therapeutic has not yet been identified. In this study, a peptoid-based mimic of the peptide KLVFF (residues 16-20 of Aβ) was tested for its ability to modulate Aβ aggregation. Peptoid JPT1 includes chiral, aromatic side chains to induce formation of a stable helical secondary structure that allows for greater interaction between the aromatic side chains and the cross β-sheet of Aβ. JPT1 was found to modulate Aβ40 aggregation, specifically decreasing lag time to β-sheet aggregate formation as well as the total number of fibrillar, β-sheet structured aggregates formed. These results suggest that peptoids may be able to limit the formation of Aβ aggregates that are associated with AD. PMID:24689364

  17. Polyalanine and Abeta Aggregation Kinetics: Probing Intermediate Oligomer Formation and Structure Using Computer Simulations

    NASA Astrophysics Data System (ADS)

    Phelps, Erin Melissa

    2011-12-01

    The aggregation of proteins into stable, well-ordered structures known as amyloid fibrils has been associated with many neurodegenerative diseases. Amyloid fibrils are long straight, and un-branched structures containing several proto-filaments, each of which exhibits "cross beta structure," -- ribbon-like layers of large beta sheets whose strands run perpendicular to the fibril axis. It has been suggested in the literature that the pathway to fibril formation has the following steps: unfolded monomers associate into transient unstable oligomers, the oligomers undergo a rearrangement into the cross-beta structure and form into proto-filaments, these proto-filaments then associate and grow into fully formed fibrils. Recent experimental studies have determined that the unstable intermediate structures are toxic to cells and that their presence may play a key role in the pathogenesis of the amyloid diseases. Many efforts have been made to determine the structure of intermediate oligomer aggregates that form during the fibrillization process. The goal of this work is to provide details about the structure and formation kinetics of the unstable oligomers that appear in the fibril formation pathway. The specific aims of this work are to determine the steps in the fibril formation pathway and how the kinetics of fibrillization changes with variations in temperature and concentration. The method used is the application of discontinuous molecular dynamics to large systems of peptides represented with an intermediate resolution model, PRIME, that was previously developed in our group. Three different peptide sequences are simulated: polyalanine (KA14K), Abeta17-40, and Abeta17-42; the latter two are truncated sequences of the Alzheimer's peptide. We simulate the spontaneous assembly of these peptide chains from a random initial configuration of random coils. We investigate aggregation kinetics and oligomer formation of a system of 192 polyalanine (KA14K) chains over a

  18. A calorimetric determination of the enthalpy of formation and a description of the defect structure of the ordered beta-phase /Ni, Cu/ /1-x/ Al/x/

    NASA Technical Reports Server (NTRS)

    Henig, E. T.; Lukas, H. L.

    1988-01-01

    In order to describe thermodynamically the defect structure of an ordered B-Hume-Rothery phase, the heat of formation of (Ni,Cu)(1-x)Al(x) was measured at 1100 K as a function of concentration in the range x (sub Al) = 0.4 and 0.55 for three substitution rations x (sub Ni)/x (sub Cu) = infinity; 11; 5. The heat of formation of the NiAl beta-phase is strongly negative. For the stoichiometric composition it is -72.2 kJ/g-atom. On both the nickel-rich side and the aluminum-rich side the magnitude of the enthalpy of formation decreases linearly with concentration. Substitution of nickel for copper decreases the magnitude of the enthalpy of formation over the entire homogeneity range for the phase (Ni,Cu)(1-x)Al(x). The curve for the enthalpy of formation as well as the literature values for the chemical potential of aluminum are described with great accuracy by the disorder model of Wagner-Schottky.

  19. A Theoretical Model of a Thinning Current Sheet in the Low-β Plasmas

    NASA Astrophysics Data System (ADS)

    Takeshige, Satoshi; Takasao, Shinsuke; Shibata, Kazunari

    2015-07-01

    Magnetic reconnection is an important physical process in various explosive phenomena in the universe. In previous studies, it was found that fast reconnection takes place when the thickness of a current sheet becomes on the order of a microscopic length such as the ion Larmor radius or the ion inertial length. In this study, we investigated the pinching process of a current sheet by the Lorentz force in a low-β plasma using one-dimensional magnetohydrodynamics (MHD) simulations. It is known that there is an exact self-similar solution for this problem that neglects gas pressure. We compared the non-linear MHD dynamics with the analytic self-similar solution. From the MHD simulations, we found that with the gas pressure included the implosion process deviates from the analytic self-similar solution as t\\to {t}0, where t0 is the explosion time when the thickness of a current sheet of the analytic solution becomes 0. We also found that a pair of MHD fast-mode shocks is generated and propagates after the formation of the pinched current sheet as t\\to {t}0. On the basis of the Rankine-Hugoniot relations, we derived the scaling law of the physical quantities with respect to the initial plasma beta in the pinched current sheet. Our study could help us estimate the physical quantities in the pinched current sheet formed in a low-β plasma.

  20. Beta amyloid and hyperphosphorylated tau deposits in the pancreas in type 2 diabetes

    SciTech Connect

    Miklossy, J.; Miller, L.; Qing, H.; Radenovic, A.; Kis, A.; Vileno, B.; Laszlo, F.; Martins, R.N.; Waeber, G.; Mooser, V.; Bosman, F.; Khalili, K.; Darbinian, N.; McGeer, P.L.

    2008-08-25

    Strong epidemiologic evidence suggests an association between Alzheimer disease (AD) and type 2 diabetes. To determine if amyloid beta (A{beta}) and hyperphosphorylated tau occurs in type 2 diabetes, pancreas tissues from 21 autopsy cases (10 type 2 diabetes and 11 controls) were analyzed. APP and tau mRNAs were identified in human pancreas and in cultured insulinoma beta cells (INS-1) by RT-PCR. Prominent APP and tau bands were detected by Western blotting in pancreatic extracts. Aggregated A{beta}, hyperphosphorylated tau, ubiquitin, apolipoprotein E, apolipoprotein(a), IB1/JIP-1 and JNK1 were detected in Langerhans islets in type 2 diabetic patients. A{beta} was co-localized with amylin in islet amyloid deposits. In situ beta sheet formation of islet amyloid deposits was shown by infrared microspectroscopy (SIRMS). LPS increased APP in non-neuronal cells as well. We conclude that A{beta} deposits and hyperphosphorylated tau are also associated with type 2 diabetes, highlighting common pathogenetic features in neurodegenerative disorders, including AD and type 2 diabetes and suggesting that A{beta} deposits and hyperphosphorylated tau may also occur in other organs than the brain.

  1. Hydroxylated metabolites of beta- and delta-hexachlorocyclohexane: bacterial formation, stereochemical configuration, and occurrence in groundwater at a former production site.

    PubMed

    Raina, Vishakha; Hauser, Andrea; Buser, Hans Rudolf; Rentsch, Daniel; Sharma, Poonam; Lal, Rup; Holliger, Christof; Poiger, J Thomas; Müller, Markus D; Kohler, Hans-Peter E

    2007-06-15

    Although the use of hexachlorocyclohexane (HCH), one of the most popular insecticides after the Second World War, has been discontinued in many countries, problems remain from former production and waste sites. Despite the widespread occurrence of HCHs, the environmental fate of these compounds is not fully understood. In particular, environmental metabolites of the more persistent beta-HCH and delta-HCH have not been fully identified. Such knowledge, however, is important to follow degradation and environmental fate of the HCHs. In the present study, several hydroxy metabolites that formed during incubation of beta- and delta-HCH with the common soil microorganism Sphingobium indicum B90A were isolated, characterized, and stereochemically identified by gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance spectroscopy (NMR). The metabolites were identified as isomeric pentachlorocyclohexanols (B1, D1) and tetrachlorocyclohexane-1,4-diols (B2, D2); delta-HCH additionally formed a tetrachloro-2-cyclohexen-1-ol (D3) and a trichloro-2-cyclohexene-1,4-diol (D4), most likely by hydroxylation of delta-pentachlorocyclohexene (delta-PCCH), initially formed by dehydrochlorination. The dehydrochlorinase LinA was responsible for conversion of delta-HCH into delta-PCCH, and the haloalkane dehalogenase LinB was responsible for the transformation of beta-HCH and delta-HCH into B1 and D1, respectively, and subsequently into B2 and D2, respectively. LinB was also responsible for transforming delta-PCCH into D3 and subsequently into D4. These hydroxylations proceeded in accordance with SN2 type reactions with initial substitution of equatorial Cls and formation of axially hydroxylated stereoisomers. The apparently high reactivity of equatorial Cls in beta- and delta-HCH toward initial hydroxylation by LinB of Sphingobium indicum B90A is remarkable when considering the otherwise usually higher reactivity of axial Cls. Several of these metabolites were detected

  2. Sfrp1, Sfrp2, and Sfrp5 regulate the Wnt/beta-catenin and the planar cell polarity pathways during early trunk formation in mouse.

    PubMed

    Satoh, Wataru; Matsuyama, Makoto; Takemura, Hiromasa; Aizawa, Shinichi; Shimono, Akihiko

    2008-02-01

    Sfrp is a secreted Wnt antagonist that directly interacts with Wnt ligand. We show here that inactivation of Sfrp1, Sfrp2, and Sfrp5 leads to fused somites formation in early-somite mouse embryos, simultaneously resulting in defective convergent extension (CE), which causes severe shortening of the anteroposterior axis. These observations indicate the redundant roles of Sfrp1, Sfrp2, and Sfrp5 in early trunk formation. The roles of the Sfrps were genetically distinguished in terms of the regulation of Wnt pathways. Genetic analysis combining Sfrps mutants and Loop-tail mice revealed the involvement of Sfrps in CE through the regulation of the planar cell polarity pathway. Furthermore, Dkk1-deficient embryos carrying Sfrp1 homozygous and Sfrp2 heterozygous mutations display irregular somites and indistinct intersomitic boundaries, which indicates that Sfrps-mediated inhibition of the Wnt/beta-catenin pathway is necessary for somitogenesis. Our results suggest that Sfrps regulation of the canonical and noncanonical pathways is essential for proper trunk formation. PMID:18257070

  3. Overexpression of protein kinase C. beta. 1 enhances phospholipase D activity and diacylglycerol formation in phorbol ester-stimulated rat fibroblasts

    SciTech Connect

    Pai, Jinkeon; Pachter, J.A.; Bishop, W.R. ); Weinstein, I.B. )

    1991-01-15

    The authors are using a Rat-6 fibroblast cell line that stably overexpresses the {beta}1 isozyme of protein kinase C (PKC) to study regulation of phospholipid hydrolysis by PKC. Stimulation of control (R6-C1) or overexpressing (R6-PKC3) cells with phorbol ester results in an increase in diacylglycerol (DAG) mass with no increase in inositol phosphates, indicating that DAG is not formed by inositol phospholipid breakdown. A more dramatic DAG increase occurs in R6-PKC3 cells compared to R6-C1 cells. To further define the source of DAG, phosphatidylcholine (PC) pools were labeled with ({sup 3}H)myristic acid or with ({sup 3}H)- or ({sup 32}P)alkyllyso-PC and formation of labeled phosphatidylethanol, an unambiguous marker of phospholipase D activation, was monitored. Phorbol ester-stimulated phosphatidylethanel formation is 5-fold greater in the R6-PKC3 cell line. Formation of radiolabeled phosphatidic acid (PA) is also enhanced by PKC overepression. In cells double-labeled with ({sup 3}H)- and ({sup 32}P)-alkyl-lysoPC, the {sup 3}H/{sup 32}P ratio of PA and PC are identical 15 min after stimulation, suggesting that a phospholipase D mechanism predominates. These results indicate that phospholipase D is regulated by the action of PKC. Enhanced phospholipase D activity may contribute to the growth abnormalities seen in PKC-overexpressing cells.

  4. The part of a long beta hairpin from the scrapie form of the human prion protein is reconstructed in the synthetic CC36 protein.

    PubMed

    Khrustalev, Vladislav Victorovich; Khrustaleva, Tatyana Aleksandrovna; Szpotkowski, Kamil; Poboinev, Victor Vitoldovich; Kakhanouskaya, Katsiaryna Yurieuna

    2016-10-01

    Mechanisms of beta sheet formation by the human prion protein are not clear yet. In this work, we clarified the role of the region containing C-half of the second helix and N-half of the third helix of that protein in the process of alpha helix to beta sheet transition. Solid phase automatic synthesis of the original peptide (CC36: Cys179-Cys214) failed because of the beta hairpin formation in the region 206-MERVVEQMC-214 with a high beta strand potential. Using Met206Arg and Val210Arg substitutions, we increased the probability of alpha helix formation by that sequence. After that modification, the complete CC36 peptide with disulfide bond has been synthesized. Modified peptide has been studied by circular dichroism (CD) and fluorescence spectrography. According to the CD spectra analysis, the CC36 peptide contains 37% of residues in beta sheet and just 15% in helix. Thermal analysis under the control of CD shows that the secondary structure content of the peptide is stable from 5°C to 80°C. Dissociation of oligomers of the CC36 peptide finishes at 37°C according to the fluorescence analysis. The CC36 peptide is able to bind Mn(2+) cations, which causes small temperature-associated structural shifts at concentrations of 2 - 10·10(-6) M. Predicted beta hairpin of the CC36 peptide (two beta strands are: 184-IKQHTVT-190 and 197-TETDVKM-205) should be the part of a longer beta hairpin from the scrapie form of the prion protein (PrPSc). Analogs of the CC36 peptide may be considered as antigens for the future development of a vaccine against PrPSc. Proteins 2016; 84:1462-1479. © 2016 Wiley Periodicals, Inc. PMID:27317933

  5. Ablation of MMP9 gene ameliorates paracellular permeability and fibrinogen-amyloid beta complex formation during hyperhomocysteinemia.

    PubMed

    Muradashvili, Nino; Tyagi, Reeta; Metreveli, Naira; Tyagi, Suresh C; Lominadze, David

    2014-09-01

    Increased blood level of homocysteine (Hcy), called hyperhomocysteinemia (HHcy) accompanies many cognitive disorders including Alzheimer's disease. We hypothesized that HHcy-enhanced cerebrovascular permeability occurs via activation of matrix metalloproteinase-9 (MMP9) and leads to an increased formation of fibrinogen-β-amyloid (Fg-Aβ) complex. Cerebrovascular permeability changes were assessed in C57BL/6J (wild type, WT), cystathionine-β-synthase heterozygote (Cbs+/-, a genetic model of HHcy), MMP9 gene knockout (Mmp9-/-), and Cbs and Mmp9 double knockout (Cbs+/-/Mmp9-/-) mice using a dual-tracer probing method. Expression of vascular endothelial cadherin (VE-cadherin) and Fg-Aβ complex formation was assessed in mouse brain cryosections by immunohistochemistry. Short-term memory of mice was assessed with a novel object recognition test. The cerebrovascular permeability in Cbs+/- mice was increased via mainly the paracellular transport pathway. VE-cadherin expression was the lowest and Fg-Aβ complex formation was the highest along with the diminished short-term memory in Cbs+/- mice. These effects of HHcy were ameliorated in Cbs+/-/Mmp9-/- mice. Thus, HHcy causes activation of MMP9 increasing cerebrovascular permeability by downregulation of VE-cadherin resulting in an enhanced formation of Fg-Aβ complex that can be associated with loss of memory. These data may lead to the identification of new targets for therapeutic intervention that can modulate HHcy-induced cerebrovascular permeability and resultant pathologies. PMID:24865997

  6. Transforming Growth Factor Beta Signaling Is Essential for the Autonomous Formation of Cartilage-Like Tissue by Expanded Chondrocytes

    PubMed Central

    Tekari, Adel; Luginbuehl, Reto; Hofstetter, Willy; Egli, Rainer J.

    2015-01-01

    Cartilage is a tissue with limited self-healing potential. Hence, cartilage defects require surgical attention to prevent or postpone the development of osteoarthritis. For cell-based cartilage repair strategies, in particular autologous chondrocyte implantation, articular chondrocytes are isolated from cartilage and expanded in vitro to increase the number of cells required for therapy. During expansion, the cells lose the competence to autonomously form a cartilage-like tissue, that is in the absence of exogenously added chondrogenic growth factors, such as TGF-βs. We hypothesized that signaling elicited by autocrine and/or paracrine TGF-β is essential for the formation of cartilage-like tissue and that alterations within the TGF-β signaling pathway during expansion interfere with this process. Primary bovine articular chondrocytes were harvested and expanded in monolayer culture up to passage six and the formation of cartilage tissue was investigated in high density pellet cultures grown for three weeks. Chondrocytes expanded for up to three passages maintained the potential for autonomous cartilage-like tissue formation. After three passages, however, exogenous TGF-β1 was required to induce the formation of cartilage-like tissue. When TGF-β signaling was blocked by inhibiting the TGF-β receptor 1 kinase, the autonomous formation of cartilage-like tissue was abrogated. At the initiation of pellet culture, chondrocytes from passage three and later showed levels of transcripts coding for TGF-β receptors 1 and 2 and TGF-β2 to be three-, five- and five-fold decreased, respectively, as compared to primary chondrocytes. In conclusion, the autonomous formation of cartilage-like tissue by expanded chondrocytes is dependent on signaling induced by autocrine and/or paracrine TGF-β. We propose that a decrease in the expression of the chondrogenic growth factor TGF-β2 and of the TGF-β receptors in expanded chondrocytes accounts for a decrease in the activity of

  7. Multi-frequency characterization of radar backscatter and the formation of ice layers in the southeast percolation area of the Greenland ice sheet

    NASA Astrophysics Data System (ADS)

    Miller, J.; Forster, R. R.; Box, J. E.; Long, D. G.

    2012-12-01

    The relationship between radar backscatter and the formation of ice layers in the southeast percolation area of the Greenland ice sheet is explored using two scatterometer data sets, 1999-2009 data acquired from NASA's Ku-band SeaWinds scatterometer on the QuikSCAT satellite (QSCAT), and 2009 data acquired from ESA's C-band advanced scatterometer (ASCAT) on the MetOp satellite, together with 1999-2009 annually dated ice layers from five firn cores acquired during the 2010 and 2011 Arctic Circle Traverse (ACT) campaigns. Snowpack stratigraphy within the southeast percolation area is complex and forms as the result of the seasonal progression of snow accumulation at the surface followed by melt water infiltration. Melt water may be retained in liquid form, or refreeze which creates scattering layers embedded within snow and firn layers at differing depths. Ice layers are created by shallow infiltration and refreezing of melt water at the surface or by downward percolation and lateral infiltration and refreezing of melt water at depth. Ice layers are spatially continuous over large areas and identified in firn core data. Ice pipes, lenses, and glands are created by the downward percolation of melt water at point locations, which subsequently refreezes at depth within percolation channels. Ice pipes, lenses, and glands are spatially discontinuous and rarely identified in firn core data, however, contribute to the microwave response as observed over the large-scale antenna footprint of a satellite- bourne scatterometer. Microwave signatures within this region exhibit what appear to be distinct seasonal responses to melt and refreeze events resulting in the formation of scattering layers within the snowpack, in the form of rapid relative increases and decreases in backscatter measurements followed by a step response in the signal. Two backscatter models identifying both the timing and spatial extent of the given parameter are derived from the observed responses: 1) a

  8. Neuroprotective approaches in experimental models of beta-amyloid neurotoxicity: relevance to Alzheimer's disease.

    PubMed

    Harkany, T; Hortobágyi, T; Sasvári, M; Kónya, C; Penke, B; Luiten, P G; Nyakas, C

    1999-08-01

    critical role for N-methyl-D-aspartate (NMDA) receptors was postulated in the neurotoxic processes. Additionally, A beta s might become internalized, either after their selective binding to cell-surface receptors or after membrane association in consequence of their highly lipophilic nature, and induce free radical generation and subsequent oxidative injury. Ca(2+)-mediated neurotoxic events and generation of oxygen free radicals may indeed potentiate each other, or even converge to the same neurotoxic events, leading to cell death. 6. Neuroprotection against A beta toxicity was achieved by both pre- and post-treatment with NMDA receptor channel antagonists. Moreover, direct radical-scavengers, such as vitamin E or vitamin C, attenuated A beta toxicity with high efficacy. Interestingly, combined drug treatments did not necessarily result in additive enhanced neuroprotection. 7. Similarly to the blockade of NMDA receptors, the neurotoxic action of A beta s could be markedly decreased by pharmacological manipulation of voltage-dependent Ca(2+)-channels, serotonergic IA or adenosine A1 receptors, and by drugs eliciting membrane hyperpolarization or indirect blockade of Ca(2+)-mediated intracellular consequences of intracerebral A beta infusions. 8. A beta neurotoxicity might be dose-dependently modulated by trace metals. In spite of the fact that zinc (Zn) may act as a potent inhibitor of the NMDA receptor channel, high Zn doses accelerate A beta fibril formation, stabilize the beta-sheet conformation and thereby potentiate A beta neurotoxicity. Combined trace element supplementation with Se, Mn, or Mg, which prevails over the expression of detoxifying enzymes or counteracts intracellular elevations of Ca2+, may reduce the neurotoxic impact of A beta s. 9. Alterations in the regulatory functions of the hypothalamo-pituitary-adrenal axis may contribute significantly to neurodegenerative changes in the brain. Furthermore, AD patients exhibit substantially increased circadia

  9. Soluble amyloid beta oligomers block the learning-induced increase in hippocampal sharp wave-ripple rate and impair spatial memory formation.

    PubMed

    Nicole, Olivier; Hadzibegovic, Senka; Gajda, Judyta; Bontempi, Bruno; Bem, Tiaza; Meyrand, Pierre

    2016-01-01

    Post-learning hippocampal sharp wave-ripples (SWRs) generated during slow wave sleep are thought to play a crucial role in memory formation. While in Alzheimer's disease, abnormal hippocampal oscillations have been reported, the functional contribution of SWRs to the typically observed spatial memory impairments remains unclear. These impairments have been related to degenerative synaptic changes produced by soluble amyloid beta oligomers (Aβos) which, surprisingly, seem to spare the SWR dynamics during routine behavior. To unravel a potential effect of Aβos on SWRs in cognitively-challenged animals, we submitted vehicle- and Aβo-injected mice to spatial recognition memory testing. While capable of forming short-term recognition memory, Aβ mice exhibited faster forgetting, suggesting successful encoding but an inability to adequately stabilize and/or retrieve previously acquired information. Without prior cognitive requirements, similar properties of SWRs were observed in both groups. In contrast, when cognitively challenged, the post-encoding and -recognition peaks in SWR occurrence observed in controls were abolished in Aβ mice, indicating impaired hippocampal processing of spatial information. These results point to a crucial involvement of SWRs in spatial memory formation and identify the Aβ-induced impairment in SWRs dynamics as a disruptive mechanism responsible for the spatial memory deficits associated with Alzheimer's disease. PMID:26947247

  10. Soluble amyloid beta oligomers block the learning-induced increase in hippocampal sharp wave-ripple rate and impair spatial memory formation

    PubMed Central

    Nicole, Olivier; Hadzibegovic, Senka; Gajda, Judyta; Bontempi, Bruno; Bem, Tiaza; Meyrand, Pierre

    2016-01-01

    Post-learning hippocampal sharp wave-ripples (SWRs) generated during slow wave sleep are thought to play a crucial role in memory formation. While in Alzheimer’s disease, abnormal hippocampal oscillations have been reported, the functional contribution of SWRs to the typically observed spatial memory impairments remains unclear. These impairments have been related to degenerative synaptic changes produced by soluble amyloid beta oligomers (Aβos) which, surprisingly, seem to spare the SWR dynamics during routine behavior. To unravel a potential effect of Aβos on SWRs in cognitively-challenged animals, we submitted vehicle- and Aβo-injected mice to spatial recognition memory testing. While capable of forming short-term recognition memory, Aβ mice exhibited faster forgetting, suggesting successful encoding but an inability to adequately stabilize and/or retrieve previously acquired information. Without prior cognitive requirements, similar properties of SWRs were observed in both groups. In contrast, when cognitively challenged, the post-encoding and -recognition peaks in SWR occurrence observed in controls were abolished in Aβ mice, indicating impaired hippocampal processing of spatial information. These results point to a crucial involvement of SWRs in spatial memory formation and identify the Aβ-induced impairment in SWRs dynamics as a disruptive mechanism responsible for the spatial memory deficits associated with Alzheimer’s disease. PMID:26947247

  11. Nuclear magnetic resonance evidence for the dimer formation of beta amyloid peptide 1-42 in 1,1,1,3,3,3-hexafluoro-2-propanol.

    PubMed

    Shigemitsu, Yoshiki; Iwaya, Naoko; Goda, Natsuko; Matsuzaki, Mizuki; Tenno, Takeshi; Narita, Akihiro; Hoshi, Minako; Hiroaki, Hidekazu

    2016-04-01

    Alzheimer's disease involves accumulation of senile plaques in which filamentous aggregates of amyloid beta (Aβ) peptides are deposited. Recent studies demonstrate that oligomerization pathways of Aβ peptides may be complicated. To understand the mechanisms of Aβ(1-42) oligomer formation in more detail, we have established a method to produce (15)N-labeled Aβ(1-42) suited for nuclear magnetic resonance (NMR) studies. For physicochemical studies, the starting protein material should be solely monomeric and all Aβ aggregates must be removed. Here, we succeeded in fractionating a "precipitation-resistant" fraction of Aβ(1-42) from an "aggregation-prone" fraction by high-performance liquid chromatography (HPLC), even from bacterially overexpressed Aβ(1-42). However, both Aβ(1-42) fractions after 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) treatment formed amyloid fibrils. This indicates that the "aggregation seed" was not completely monomerized during HFIP treatment. In addition, Aβ(1-42) dissolved in HFIP was found to display a monomer-dimer equilibrium, as shown by two-dimensional (1)H-(15)N NMR. We demonstrated that the initial concentration of Aβ during the HFIP pretreatment altered the kinetic profiles of Aβ fibril formation in a thioflavin T fluorescence assay. The findings described here should ensure reproducible results when studying the Aβ(1-42) peptide. PMID:26772162

  12. Molecular basis for amyloid-[beta] polymorphism

    SciTech Connect

    Colletier, Jacques-Philippe; Laganowsky, Arthur; Landau, Meytal; Zhao, Minglei; Soriaga, Angela B.; Goldschmidt, Lukasz; Flot, David; Cascio, Duilio; Sawaya, Michael R.; Eisenberga, David

    2011-10-19

    Amyloid-beta (A{beta}) aggregates are the main constituent of senile plaques, the histological hallmark of Alzheimer's disease. A{beta} molecules form {beta}-sheet containing structures that assemble into a variety of polymorphic oligomers, protofibers, and fibers that exhibit a range of lifetimes and cellular toxicities. This polymorphic nature of A{beta} has frustrated its biophysical characterization, its structural determination, and our understanding of its pathological mechanism. To elucidate A{beta} polymorphism in atomic detail, we determined eight new microcrystal structures of fiber-forming segments of A{beta}. These structures, all of short, self-complementing pairs of {beta}-sheets termed steric zippers, reveal a variety of modes of self-association of A{beta}. Combining these atomic structures with previous NMR studies allows us to propose several fiber models, offering molecular models for some of the repertoire of polydisperse structures accessible to A{beta}. These structures and molecular models contribute fundamental information for understanding A{beta} polymorphic nature and pathogenesis.

  13. Structural model of the amyloid fibril formed by beta(2)-microglobulin #21-31 fragment based on vibrational spectroscopy.

    PubMed

    Hiramatsu, Hirotsugu; Goto, Yuji; Naiki, Hironobu; Kitagawa, Teizo

    2005-06-01

    A structural model of amyloid fibril formed by the #21-31 fragment of beta2-microglobulin is proposed from microscope IR measurements on specifically 13C-labeled peptide fibrils and Raman spectra of the dispersed fibril solution. The 13C-shifted amide frequency indicated the secondary structure of the labeled residues. The IR spectra have demonstrated that the region between F22 and V27 forms the core part with the extended beta-sheet structure. Raman spectra indicated the formation of a dimer with a disulfide bridge between C25 residues.

  14. Solid-state NMR analysis of the {beta}-strand orientation of the protofibrils of amyloid {beta}-protein

    SciTech Connect

    Doi, Takashi; Masuda, Yuichi; Irie, Kazuhiro; Akagi, Ken-ichi; Monobe, Youko; Imazawa, Takayoshi; Takegoshi, K.

    2012-11-30

    Highlights: Black-Right-Pointing-Pointer The supramolecular structure of A{beta}42 protofibrils was analyzed by solid-state NMR. Black-Right-Pointing-Pointer The Ala-21 residue in the A{beta}42 protofibrils is included in a slightly disordered {beta}-strand. Black-Right-Pointing-Pointer The A{beta}42 protofibrils do not form intermolecular in-register parallel {beta}-sheets. -- Abstract: Alzheimer's disease (AD) is caused by abnormal deposition (fibrillation) of a 42-residue amyloid {beta}-protein (A{beta}42) in the brain. During the process of fibrillation, the A{beta}42 takes the form of protofibrils with strong neurotoxicity, and is thus believed to play a crucial role in the pathogenesis of AD. To elucidate the supramolecular structure of the A{beta}42 protofibrils, the intermolecular proximity of the Ala-21 residues in the A{beta}42 protofibrils was analyzed by {sup 13}C-{sup 13}C rotational resonance experiments in the solid state. Unlike the A{beta}42 fibrils, an intermolecular {sup 13}C-{sup 13}C correlation was not found in the A{beta}42 protofibrils. This result suggests that the {beta}-strands of the A{beta}42 protofibrils are not in an in-register parallel orientation. A{beta}42 monomers would assemble to form protofibrils with the {beta}-strand conformation, then transform into fibrils by forming intermolecular parallel {beta}-sheets.

  15. Helix-forming tendencies of amino acids depend on their sequence contexts: tripeptides AFG and FAG show incipient beta-bulge formation in their crystal structures.

    PubMed

    Parthasarathy, R; Go, K; Chaturvedi, S

    1993-01-01

    Many of the theoretical methods used for predicting the occurrence of alpha-helices in peptides are based on the helical preferences of amino acid monomer residues. In order to check whether the helix-forming tendencies are based on helical preferences of monomers only or also on their sequence contexts, we synthesized permuted sequences of the tripeptides GAF, GAV, and GAL that formed crystalline helices with near alpha-helical conformation. The tripeptides AFG and FAG formed good crystals. The x-ray crystallographic studies of AFG and FAG showed that though they contain the same amino acids as GAF but in different sequences, they do not assume a helical conformation in the solid state. On the other hand, AFG and FAG, which contain the same amino acids but in a different sequence, exhibit nearly the same backbone torsion angles corresponding to an incipient formation of a beta-bulge, and exhibit nearly identical unit cells and crystal structures. Based on these results, it appears that the helix-forming tendencies of amino acids depend on the sequence context in which it occurs in a polypeptide. The synthetic peptides AFG (L-Ala-L-Phe-Gly) and FAG (L-Phe-L-Ala-Gly), C14H19N3O4, crystallize in the orthorhombic space group P2(1)2(1)2(1), with a = 5.232(1), b = 14.622(2), c = 19.157(3) A, Dx = 1.329 g cm-3, Z = 4, R = 0.041 for 549 reflections for AFG, and with a = 5.488(2), b = 14.189(1), c = 18.562(1) A, Dx = 1.348 g cm-3, Z = 4, R = 0.038 for 919 reflections for FAG. Unlike the other tripeptides GAF, GGV, GAL, and GAI, the crystals of AFG and FAG do not contain water molecule, and the molecules of AFG aor FAG do not show the helical conformation. The torsion angles at the backbone of the peptide are psi 1 = 144.5(5) degrees; phi 2, psi 2 = -98.1(6) degrees, -65.2(6) degrees; phi 3, psi 13, psi 31 = 154.1(6) degrees, -173.6(6) degrees, 6.9(8) degrees for AFG; and psi 1 = 162.6(3) degrees; phi 2, psi 2 = -96.7(4) degrees, -46.3(4) degrees; phi 3, psi 13, psi 31

  16. Interaction between beta-Purothionin and dimyristoylphosphatidylglycerol: a (31)P-NMR and infrared spectroscopic study.

    PubMed Central

    Richard, Julie-Andrée; Kelly, Isabelle; Marion, Didier; Pézolet, Michel; Auger, Michèle

    2002-01-01

    The interaction of beta-purothionin, a small basic and antimicrobial protein from the endosperm of wheat seeds, with multilamellar vesicles of dimyristoylphosphatidylglycerol (DMPG) was investigated by (31)P solid-state NMR and infrared spectroscopy. NMR was used to study the organization and dynamics of DMPG in the absence and presence of beta-purothionin. The results indicate that beta-purothionin does not induce the formation of nonlamellar phases in DMPG. Two-dimensional exchange spectroscopy shows that beta-purothionin decreases the lateral diffusion of DMPG in the fluid phase. Infrared spectroscopy was used to investigate the perturbations, induced by beta-purothionin, of the polar and nonpolar regions of the phospholipid bilayers. At low concentration of beta-purothionin, the temperature of the gel-to-fluid phase transition of DMPG increases from 24 degrees C to ~33 degrees C, in agreement with the formation of electrostatic interactions between the cationic protein and the anionic phospholipid. At higher protein concentration, the lipid transition is slightly shifted toward lower temperature and a second transition is observed below 20 degrees C, suggesting an insertion of the protein in the hydrophobic core of the lipid bilayer. The results also suggest that the presence of beta-purothionin significantly modifies the lipid packing at the surface of the bilayer to increase the accessibility of water molecules in the interfacial region. Finally, orientation measurements indicate that the alpha-helices and the beta-sheet of beta-purothionin have tilt angles of ~60 degrees and 30 degrees, respectively, relative to the normal of the ATR crystal. PMID:12324425

  17. Synergistic Action of Fibroblast Growth Factor-2 and Transforming Growth Factor-beta1 Enhances Bioprinted Human Neocartilage Formation

    PubMed Central

    Cui, Xiaofeng; Breitenkamp, Kurt; Lotz, Martin; D’Lima, Darryl

    2012-01-01

    Bioprinting as a promising but unexplored approach for cartilage tissue engineering has the advantages of high throughput, digital control, and highly accurate placement of cells and biomaterial scaffold to the targeted 3D locations with simultaneous polymerization. This study tested feasibility of using bioprinting for cartilage engineering and examined the influence of cell density, growth and differentiation factors. Human articular chondrocytes were printed at various densities, stimulated transiently with growth factors and subsequently with chondrogenic factors. Samples were cultured for up to 4 weeks to evaluate cell proliferation and viability, mechanical properties, mass swelling ratio, water content, gene expression, ECM production, DNA content, and histology. Bioprinted samples treated with FGF-2/TGF-β1 had the best chondrogenic properties among all groups apparently due to synergistic stimulation of cell proliferation and chondrogenic phenotype. ECM production per chondrocyte in low cell density was much higher than that in high cell seeding density. This finding was also verified by mechanical testing and histology. In conclusion, cell seeding density that is feasible for bioprinting also appears optimal for human neocartilage formation when combined with appropriate growth and differentiation factors. PMID:22508498

  18. Study of formation of deep trapping mechanism by UV, beta and gamma irradiated Eu(3+) activated SrY2O4 and Y4Al2O9 phosphors.

    PubMed

    Dubey, Vikas; Kaur, Jagjeet; Parganiha, Yogita; Suryanarayana, N S; Murthy, K V R

    2016-04-01

    This paper reports the thermoluminescence properties of Eu(3+) doped different host matrix phosphors (SrY2O4 and Y4Al2O9). The phosphor is prepared by high temperature solid state reaction method. The method is suitable for large scale production and fixed concentration of boric acid using as a flux. The prepared samples were characterized by X-ray diffraction technique and the crystallite size calculated by Scherer's formula. The prepared phosphor characterized by Scanning Electron Microscopic (SEM), Fourier Transform Infrared (FTIR), Energy Dispersive X-ray analysis (EDX), thermoluminescence (TL) and Transmission Electron Microscopic (TEM) techniques. The prepared phosphors for different concentration of Eu(3+) ions were examined by TL glow curve for UV, beta and gamma irradiation. The UV 254nm source used for UV irradiation, Sr(90) source was used for beta irradiation and Co(60) source used for gamma irradiation. SrY2O4:Eu(3+)and Y4Al2O9:Eu(3+) phosphors which shows both higher temperature peaks and lower temperature peaks for UV, beta and gamma irradiation. Here UV irradiated sample shows the formation of shallow trap (surface trapping) and the gamma irradiated sample shows the formation of deep trapping. The estimation of trap formation was evaluated by knowledge of trapping parameters. The trapping parameters such as activation energy, order of kinetics and frequency factor were calculated by peak shape method. Here most of the peak shows second order of kinetics. The effect of gamma, beta and UV exposure on TL studies was also examined and it shows linear response with dose which indicate that the samples may be useful for TL dosimetry. Formation of deep trapping mechanism by UV, beta and gamma irradiated Eu(3+) activated SrY2O4 and Y4Al2O9 phosphors is discussed in this paper. PMID:26748019

  19. Discovery of DNA dyes Hoechst 34580 and 33342 as good candidates for inhibiting amyloid beta formation: in silico and in vitro study.

    PubMed

    Thai, Nguyen Quoc; Tseng, Ning-Hsuan; Vu, Mui Thi; Nguyen, Tin Trung; Linh, Huynh Quang; Hu, Chin-Kun; Chen, Yun-Ru; Li, Mai Suan

    2016-08-01

    Combining Lipinski's rule with the docking and steered molecular dynamics simulations and using the PubChem data base of about 1.4 million compounds, we have obtained DNA dyes Hoechst 34580 and Hoechst 33342 as top-leads for the Alzheimer's disease. The binding properties of these ligands to amyloid beta (Aβ) fibril were thoroughly studied by in silico and in vitro experiments. Hoechst 34580 and Hoechst 33342 prefer to locate near hydrophobic regions with binding affinity mainly governed by the van der Waals interaction. By the Thioflavin T assay, it was found that the inhibition constant IC50 ≈ 0.86 and 0.68 μM for Hoechst 34580 and Hoechst 33342, respectively. This result qualitatively agrees with the binding free energy estimated using the molecular mechanic-Poisson Boltzmann surface area method and all-atom simulations with the AMBER-f99SB-ILDN force field and water model TIP3P. In addition, DNA dyes have the high capability to cross the blood brain barrier. Thus, both in silico and in vitro experiments have shown that Hoechst 34580 and 33342 are good candidates for treating the Alzheimer's disease by inhibiting Aβ formation. PMID:27511370

  20. O-(beta-hydroxyethyl)-rutoside (Venoruton) fails to block histamine or bradykinin-induced edema formation in the canine forelimb perfused at constant arterial inflow.

    PubMed

    Dobbins, D E; Soika, C Y; Dabney, J M

    1984-10-01

    O-(beta-hydroxyethyl)-rutoside (Venoruton) has been reported to alleviate edema formation in chronic venous insufficiency. In an attempt to elucidate Venoruton's potential as an antiinflammatory agent, we infused Venoruton (20 mg/minute) intraarterially into the canine forelimb perfused at constant flow during the simultaneous intraarterial infusion of histamine (4 micrograms base/minute) or bradykinin (2 micrograms/minute). The infusion of Venoruton alone for forty minutes resulted in a small but significant increase in forelimb arterial pressures but no change in systemic pressure or forelimb skin lymph flow, protein concentration or protein transport. Subsequent infusion of either histamine or bradykinin resulted in a significant decrease in forelimb arterial pressures and a marked increase in skin lymph flow, lymph total protein concentration and lymph total protein transport. The changes in forelimb vascular pressures and skin lymph parameters were similar to those seen during the infusion of either histamine or bradykinin alone. These data indicate that the intraarterial infusion of Venoruton at this dosage does not inhibit the ability of simultaneously infused histamine or bradykinin to increase transvascular fluid and macromolecular efflux in the canine forelimb perfused at constant arterial inflow.

  1. Proteopedia: Rossmann Fold: A Beta-Alpha-Beta Fold at Dinucleotide Binding Sites

    ERIC Educational Resources Information Center

    Hanukoglu, Israel

    2015-01-01

    The Rossmann fold is one of the most common and widely distributed super-secondary structures. It is composed of a series of alternating beta strand (ß) and alpha helical (a) segments wherein the ß-strands are hydrogen bonded forming a ß-sheet. The initial beta-alpha-beta (ßaß) fold is the most conserved segment of Rossmann folds. As this segment…

  2. An experimental study of multiple zonal jet formation in rotating, thermally driven convective flows on a topographic beta-plane

    NASA Astrophysics Data System (ADS)

    Read, P. L.; Jacoby, T. N. L.; Rogberg, P. H. T.; Wordsworth, R. D.; Yamazaki, Y. H.; Miki-Yamazaki, K.; Young, R. M. B.; Sommeria, J.; Didelle, H.; Viboud, S.

    2015-08-01

    A series of rotating, thermal convection experiments were carried out on the Coriolis platform in Grenoble, France, to investigate the formation and energetics of systems of zonal jets through nonlinear eddy/wave-zonal flow interactions on a topographic β-plane. The latter was produced by a combination of a rigid, conically sloping bottom and the rotational deformation of the free upper surface. Convection was driven by a system of electrical heaters laid under the (thermally conducting) sloping bottom and led to the production of intense, convective vortices. These were observed to grow in size as each experiment proceeded and led to the development of weak but clear azimuthal jet-like flows, with a radial scale that varied according to the rotation speed of the platform. Detailed analyses reveal that the kinetic energy-weighted radial wavenumber of the zonal jets, kJy, scales quite closely either with the Rhines wavenumber as kJy ≃ 2(βT/2urms)1/2, where urms is the rms total or eddy velocity and βT is the vorticity gradient produced by the sloping topography, or the anisotropy wavenumber as k J y ≃ 1 . 25 ( βT 3 / ɛ ) 1 / 5 , where ɛ is the upscale turbulent energy transfer rate. Jets are primarily produced by the direct quasi-linear action of horizontal Reynolds stresses produced by trains of topographic Rossby waves. The nonlinear production rate of zonal kinetic energy is found to be strongly unsteady, however, with fluctuations of order 10-100 times the amplitude of the mean production rate for all cases considered. The time scale of such fluctuations is found to scale consistently with either an inertial time scale, τ p ˜ 1 . / √{ u r m s β T } , or the Ekman spin-down time scale. Kinetic energy spectra show some evidence for a k-5/3 inertial subrange in the isotropic component, suggestive of a classical Kolmogorov-Batchelor-Kraichnan upscale energy cascade and a steeper spectrum in the zonal mean flow, though not as steep as k-5, as

  3. Glacial landforms on German Bank, Scotian Shelf: evidence for Late Wisconsinan ice-sheet dynamics and implications for the formation of De Geer moraines

    USGS Publications Warehouse

    Todd, Brian J.; Valentine, Page C.; Longva, Oddvar; Shaw, John

    2007-01-01

    The extent and behaviour of the southeast margin of the Laurentide Ice Sheet in Atlantic Canada is of significance in the study of Late Wisconsinan ice sheet-ocean interactions. Multibeam sonar imagery of subglacial, ice-marginal and glaciomarine landforms on German Bank, Scotian Shelf, provides evidence of the pattern of glacial-dynamic events in the eastern Gulf of Maine. Northwest-southeast trending drumlins and megaflutes dominate northern German Bank. On southern German Bank, megaflutes of thin glacial deposits create a distinct northwest-southeast grain. Lobate regional moraines (>10km long) are concave to the northwest, up-ice direction and strike southwest-northeast, normal to the direction of ice flow. Ubiquitous, overlying De Geer moraines (

  4. Molecular analysis of T cell receptor (Ti) variable region (V) gene expression. Evidence that a single Ti beta V gene family can be used in formation of V domains on phenotypically and functionally diverse T cell populations.

    PubMed

    Acuto, O; Campen, T J; Royer, H D; Hussey, R E; Poole, C B; Reinherz, E L

    1985-06-01

    We examine the rules governing Ti beta variable (V) gene segment usage in the formation of T cell antigen-MHC receptors in diverse regulatory and effector T lymphoid subpopulations. To this end, a single Ti beta V gene family and its products were analyzed. A monoclonal antibody, termed anti-Ti3A, which was shown to be reactive with an epitope encoded by members of the REX cell line Ti beta V gene family, and which was expressed on 2% of human T lymphocytes was used in selection of clones from unprimed peripheral T lymphocytes. Both T4+, as well as T8+ T cell clones with inducer, suppressor, and/or cytotoxic function were defined. Southern analysis, isoelectric focusing and two-dimensional peptide mapping indicated that individual members of the REX V gene family were linked to different Ti beta diversity and/or joining and constant region segments. Moreover, the Ti alpha chains of such clones were distinct. These results imply that Ti beta V gene usage is not restricted to any functionally or phenotypically defined T cell subsets, and there is presumably little, if any, restriction on the mechanisms that generate combinational, junctional or chain association-mediated diversity.

  5. Beta experiment

    NASA Technical Reports Server (NTRS)

    1982-01-01

    A focused laser doppler velocimeter (LDV) system was developed for the measurement of atmospheric backscatter (beta) from aerosols at infrared wavelengths. A Doppler signal generator was used in mapping the coherent sensitive focal volume of a focused LDV system. System calibration data was analyzed during the flight test activity scheduled for the Beta system. These analyses were performed to determine the acceptability of the Beta measurement system's performance.

  6. Near-earth Thin Current Sheets and Birkeland Currents during Substorm Growth Phase

    SciTech Connect

    Sorin Zaharia; C.Z. Cheng

    2003-04-30

    Two important phenomena observed during the magnetospheric substorm growth phase are modeled: the formation of a near-Earth (|X| {approx} 9 R{sub E}) thin cross-tail current sheet, as well as the equatorward shift of the ionospheric Birkeland currents. Our study is performed by solving the 3-D force-balance equation with realistic boundary conditions and pressure distributions. The results show a cross-tail current sheet with large current (J{sub {phi}} {approx} 10 nA/m{sup 2}) and very high plasma {beta} ({beta} {approx} 40) between 7 and 10 R{sub E}. The obtained region-1 and region-2 Birkeland currents, formed on closed field lines due to pressure gradients, move equatorward and become more intense (J{sub {parallel}max} {approx} 3 {micro}A/m{sup 2}) compared to quiet times. Both results are in agreement with substorm growth phase observations. Our results also predict that the cross-tail current sheet maps into the ionosphere in the transition region between the region-1 and region-2 currents.

  7. Monoclonal antibody Cat-315 detects a glycoform of receptor protein tyrosine phosphatase beta/phosphacan early in CNS development that localizes to extrasynaptic sites prior to synapse formation.

    PubMed

    Dino, M R; Harroch, S; Hockfield, S; Matthews, R T

    2006-11-01

    Perineuronal nets (PNs) are lattice-like condensations of the extracellular matrix (ECM) that envelop synapses and decorate the surface of subsets of neurons in the CNS. Previous work has suggested that, despite the fact that PNs themselves are not visualized until later in development, some PN component molecules are expressed in the rodent CNS even before synaptogenesis. In the adult mammalian brain, monoclonal antibody Cat-315 recognizes a glycoform of aggrecan, a major component of PNs. In primary cortical cultures, a Cat-315-reactive chondroitin sulfate proteoglycan (CSPG) is also expressed on neuronal surfaces and is secreted into culture media as early as 24 h after plating. In this study, we show that in primary cortical cultures, the Cat-315 CSPG detected in early neural development is expressed in extrasynaptic sites prior to synapse formation. This suggests that ECM components in the CNS, as in the neuromuscular junction (NMJ), may prepattern neuronal surfaces prior to innervation. We further show that while the Cat-315-reactive carbohydrate decorates aggrecan in the adult, it decorates a different CSPG in the developing CNS. Using receptor protein tyrosine phosphatase beta (RPTPbeta/protein tyrosine phosphatase zeta) knock-out mice and immunoprecipitation techniques, we demonstrate here that in the developing rodent brain Cat-315 recognizes RPTPbeta isoforms. Our further examination of the Cat-315 epitope suggests that it is an O-mannose linked epitope in the HNK-1 family. The presence of the Cat-315 reactive carbohydrate on different PN components--RPTPbeta and aggrecan--at different stages of synapse development suggests a potential role for this neuron-specific carbohydrate motif in synaptogenesis.

  8. Peptide hairpins with strand segments containing alpha- and beta-amino acid residues: cross-strand aromatic interactions of facing Phe residues.

    PubMed

    Roy, Rituparna S; Gopi, Hosahudya N; Raghothama, S; Gilardi, Richard D; Karle, Isabella L; Balaram, Padmanabhan

    2005-01-01

    The incporation of beta-amino acid residues into the strand segments of designed beta-hairpin leads to the formation of polar sheets, since in the case of beta-peptide strands, all adjacent carbonyl groups point in one direction and the amide groups orient in the opposite direction. The conformational analysis of two designed peptide hairpins composed of alpha/beta-hybrid segments are described: Boc-Leu-betaPhe-Val-(D)-Pro-Gly-Leu-betaPhe-Val-OMe (1) and Boc-betaLeu-Phe-betaVal-D-Pro-Gly-betaLeu-Phe-betaVal-OMe (2). A 500-MHz 1H-NMR (nuclear magnetic resonance) analysis in methanol supports a significant population of hairpin conformations in both peptides. Diagnostic nuclear Overhauser effects (NOEs) are observed in both cases. X-ray diffraction studies on single crystals of peptide 1 reveal a beta-hairpin conformation in both the molecules, which constitute the crystallographic asymmetric unit. Three cross-strand hydrogen bonds and a nucleating type II' beta-turn at the D-Pro-Gly segment are observed in the two independent molecules. In peptide 1, the betaPhe residues at positions 2 and 7 occur at the nonhydrogen-bonding position, with the benzyl side chains pointing on opposite faces of the beta-sheet. The observed aromatic centroid-to-centroid distances are 8.92 A (molecule A) and 8.94 A (molecule B). In peptide 2, the aromatic rings must occupy facing positions in antiparallel strands, in the NMR-derived structure. Peptide 1 yields a normal "hairpin-like" CD spectrum in methanol with a minimum at 224 nm. The CD spectrum of peptide 2 reveals a negative band at 234 nm and a positive band at 221 nm, suggestive of an exciton split doublet. Modeling of the facing Phe side chains at the hydrogen-bonding position of a canonical beta-hairpin suggests that interring separation is approximately 4.78 A for the gauche+ gauche- (g+ g-) rotamer. A previously reported peptide beta-hairpin composed of only alpha-amino acids, Boc-Leu-Phe-Val-D-Pro-Gly-Leu-Phe-Val-OMe also

  9. Structural Studies of Copper(I) Complexes of Amyloid-Beta Peptide Fragments: Formation of Two-Coordinate Bis(Histidine) Complexes

    SciTech Connect

    Himes, R.A.; Park, G.Young.; Siluvai, G.Sutha.; Blackburn, N.J.; Karlin, K.D.

    2009-05-18

    The beta bind: Copper(I) binds to amyloid {beta}-peptide fragments (see structure) as a stable bis(histidine), two-coordinate, near-linear complex, even in the presence of potential additional ligands. As has been proposed or assumed in other studies, the copper(I)-peptide complexes react with dioxygen to form the reactive oxygen species H{sub 2}O{sub 2}, without the need for a third histidine ligand to promote the chemistry.

  10. IO SUBSYSTEM 1 BETA

    2002-08-21

    "IO Subsystem Ver. 1.0 Beta" uses standard object-oriented principles to minimize dependencies between the underlying input or output database format and the client code (i.e., Sierra) using the io subsystem. The interface and priciples are simolar to the Facade pattern described in the "Design Patterns" book by Gamma, et.al. The software uses data authentication algorithms to ensure data input/output is consistent with model being defined. "IO Subsystem Ver. 1.0 Beta" is a database independent input/outputmore » library for finite element analysis, preprocessing, post processing, and translation programs.« less

  11. IO SUBSYSTEM 1 BETA

    SciTech Connect

    Sjaardema, Greg

    2002-08-21

    "IO Subsystem Ver. 1.0 Beta" uses standard object-oriented principles to minimize dependencies between the underlying input or output database format and the client code (i.e., Sierra) using the io subsystem. The interface and priciples are simolar to the Facade pattern described in the "Design Patterns" book by Gamma, et.al. The software uses data authentication algorithms to ensure data input/output is consistent with model being defined. "IO Subsystem Ver. 1.0 Beta" is a database independent input/output library for finite element analysis, preprocessing, post processing, and translation programs.

  12. Free Cholesterol Induces Higher β-Sheet Content in Aβ Peptide Oligomers by Aromatic Interaction with Phe19

    PubMed Central

    2012-01-01

    Accumulating experimental evidence support an enhancing effect of free cholesterol on amyloid-beta (Aβ) aggregation. To probe the mechanisms of cholesterol-mediated Aβ aggregation, we applied all-atom molecular dynamic simulations on Aβ42 peptides in presence of free cholesterol. Several control systems were also designed to examine the specificity of cholesterol-residue interactions, including mutation on aromatic residue, substitution of cholesterol with sphingomyelin (SM) and DPPC bilayer, and a mixing SM and cholesterol. Each system was performed 4 independent simulations, with a total time of 560 ns. It was found that cholesterol increased β-sheet formation by 4 folds, but the Phe19→Ser mutation on Aβ42 peptide totally eliminated cholesterol’s effect. A stable contact was recognized between the steroid group of cholesterol and the Benzyl group of Phe19. Interestingly, our simulation revealed a regular 1 ns time interval between the establishment of cholesterol-phenylalanine contact and consequent β-sheet formation, suggesting an important role of steroid-benzyl interaction in cholesterol-mediated aggregation. The presence of SM slightly increased β-sheet formation, but the mixture of cholesterol and SM had a strong induction effect. Also, the measurement of Phe19-lipid distance indicates that aromatic side chains of peptides prone to bind to cholesterol on the surface of the mixed micelle. In the DPPC system, polar chains were attracted to the surface of membrane, yielding moderate increase of β-sheet formation. These results shed light on the mechanism of cholesterol-mediated fibrillogenesis, and help to differentiate the effects of cholesterol and other lipids on β-sheet formation process. PMID:23049991

  13. Enhanced silver ion binding to a rigid bisarene molecular cleft with formation of nonpolar pleated sheets through non-ionic intermolecular forces.

    PubMed

    Gogoll, Adolf; Polavarapu, Prasad; Grennberg, Helena

    2007-06-25

    Silver ion complexation to bisarene ligands is enhanced by providing a conformationally rigid molecular cleft in the (Z)-acenaphthylene dimer 1. NMR titrations were used to determine complexation constants K for a series of ligands in tetrahydrofuran solution, with K = 4.9 M(-1) for the Z dimer 1 and 0.4 M(-1) for the E dimer 2. Higher values of K were observed in CDCl(3)/CD(3)OD 9:1 with K = 38 M(-1) for 1 and K = 4.1 M(-1) for 2. In the solid state, isolated clusters of [1 x (AgCF(3)SO(3))(2)](2) form a novel, pleated-sheet motif based on non-ionic interactions between clusters.

  14. Maternal antioxidants prevent beta cell apoptosis and promote formation of dual hormone-expressing endocrine cells in male offspring following fetal and neonatal nicotine exposure

    PubMed Central

    BRUIN, Jennifer E; WOYNILLOWICZ, Amanda K; HETTINGA, Bart P; TARNOPOLSKY, Mark A; MORRISON, Katherine M; GERSTEIN, Hertzel C; HOLLOWAY, Alison C

    2013-01-01

    Aim Fetal and neonatal nicotine exposure causes beta cell oxidative stress and apoptosis in neonates, leading to adult-onset dysglycemia. The goal of this study was to determine whether an antioxidant intervention could prevent nicotine-induced beta cell loss. Methods Nulliparous female Wistar rats received daily subcutaneous injections of either saline or nicotine bitartrate (1.0 mg/kg/d) for 2 weeks prior to mating until weaning. Nicotine-exposed dams received either normal chow or diet containing antioxidants (1000 IU/kg vitamin E, 0.25% w/w coenzyme Q10 and 0.1% w/w alpha-lipoic acid) during mating, pregnancy and lactation; saline-exposed dams received normal chow. Pancreas tissue was collected from male offspring at 3 weeks of age to measure beta cell fraction, apoptosis, proliferation and the presence of cells co-expressing insulin and glucagon. Results The birth weight of the offspring born to nicotine-exposed dams receiving dietary antioxidants was significantly reduced. Most interestingly, the antioxidant intervention to nicotine-exposed dams prevented the beta cell loss and apoptosis observed in nicotine exposed male offspring whose mothers did not receive antioxidants. Male pups born to nicotine-treated mothers receiving antioxidants also had a trend towards increased beta cell proliferation and a significant increase in islets containing insulin/glucagon bi-hormonal cells relative to the other two treatment groups. Conclusion This study demonstrates that exposure to maternal antioxidants protects beta cells from the damaging effects of nicotine thus preserving beta cell mass. PMID:22385833

  15. Experimental Study of Lower-hybrid Drift Turbulence in a Reconnecting Current Sheet

    SciTech Connect

    Carter, T. A.; Yamada, M.; Ji, H.; Kulsrud, R. M.; Trintchouck, F.

    2002-06-18

    The role of turbulence in the process of magnetic reconnection has been the subject of a great deal of study and debate in the theoretical literature. At issue in this debate is whether turbulence is essential for fast magnetic reconnection to occur in collisionless current sheets. Some theories claim it is necessary in order to provide anomalous resistivity, while others present a laminar fast reconnection mechanism based on the Hall term in the generalized Ohm's law. In this work, a thorough study of electrostatic potential fluctuations in the current sheet of the Magnetic Reconnection Experiment (MRX) [M. Yamada et al., Phys. Plasmas 4, 1936 (1997)] was performed in order to ascertain the importance of turbulence in a laboratory reconnection experiment. Using amplified floating Langmuir probes, broadband fluctuations in the lower hybrid frequency range (fLH approximately 5-15 MHz) were measured which arise with the formation of the current sheet in MRX. The frequency spectrum, spatial amplitude profile, and spatial correlation characteristics of the measured turbulence were examined carefully, finding consistency with theories of the lower-hybrid drift instability (LHDI). The LHDI and its role in magnetic reconnection has been studied theoretically for decades, but this work represents the first detection and detailed study of the LHDI in a laboratory current sheet. The observation of the LHDI in MRX has provided the unique opportunity to uncover the role of this instability in collisionless reconnection. It was found that: (1) the LHDI fluctuations are confined to the low-beta edge of current sheets in MRX; (2) the LHDI amplitude does not correlate well in time or space with the reconnection electric field, which is directly related to the rate of reconnection; and (3) significant LHDI amplitude persists in high collisionality current sheets where the reconnection rate is classical. These findings suggest that the measured LHDI fluctuations do not play an

  16. Secondary structure formation in peptide amphiphile micelles

    NASA Astrophysics Data System (ADS)

    Tirrell, Matthew

    2012-02-01

    Peptide amphiphiles (PAs) are capable of self-assembly into micelles for use in the targeted delivery of peptide therapeutics and diagnostics. PA micelles exhibit a structural resemblance to proteins by having folded bioactive peptides displayed on the exterior of a hydrophobic core. We have studied two factors that influence PA secondary structure in micellar assemblies: the length of the peptide headgroup and amino acids closest to the micelle core. Peptide length was systematically varied using a heptad repeat PA. For all PAs the addition of a C12 tail induced micellization and secondary structure. PAs with 9 amino acids formed beta-sheet interactions upon aggregation, whereas the 23 and 30 residue peptides were displayed in an apha-helical conformation. The 16 amino acid PA experienced a structural transition from helix to sheet, indicating that kinetics play a role in secondary structure formation. A p53 peptide was conjugated to a C16 tail via various linkers to study the effect of linker chemistry on PA headgroup conformation. With no linker the p53 headgroup was predominantly alpha helix and a four alanine linker drastically changed the structure of the peptide headgroup to beta-sheet, highlighting the importance of hydrogen boding potential near the micelle core.

  17. Electron Diffraction Evidence for the Ordering of Excess Nickel Atoms by Relation to Stoichiometry in Nickel-Rich Beta'-Nial Formation of a Nickel-Aluminum (Ni2al) Superlattices

    NASA Technical Reports Server (NTRS)

    Reynaud, F.

    1988-01-01

    In electron diffraction patterns of nickel-rich beta-NiAl alloys, many anomalies are observed. One of these is the appearance of diffuse intensity maxima between the reflexions of the B2 structure. This is explained by the short-range ordering of the excess nickel atoms on the simple cubic sublattice occupied only by aluminum atoms in the stoichiometric, perfectly ordered NiAl alloy. After annealing Ni 37.5 atomic percent Al and Ni 37.75 atomic percent Al for 1 week at 300 and 400 C, the diffuse intensity maxima transformed into sharp superstructure reflexions. These reflexions are explained by the formation of the four possible variants of an ordered hexagonal superstructure corresponding to the Ni2Al composition. This structure is closely related to the Ni2Al3 structure (same space group) formed by the ordering of vacancies on the nickel sublattice in aluminum-rich beta-NiAl alloys.

  18. Identification, classification, and analysis of beta-bulges in proteins.

    PubMed Central

    Chan, A. W.; Hutchinson, E. G.; Harris, D.; Thornton, J. M.

    1993-01-01

    A beta-bulge is a region of irregularity in a beta-sheet involving two beta-strands. It usually involves two or more residues in the bulged strand opposite to a single residue on the adjacent strand. These irregularities in beta-sheets were identified and classified automatically, extending the definition of beta-bulges given by Richardson et al. (Richardson, J.S., Getzoff, E.D., & Richardson, D.C., 1978, Proc. Natl. Acad. Sci. USA 75, 2574-2578). A set of 182 protein chains (170 proteins) was used, and a total of 362 bulges were extracted. Five types of beta-bulges were found: classic, G1, wide, bent, and special. Their characteristic amino acid preferences were found for most classes of bulges. Basically, bulges occur frequently in proteins; on average there are more than two bulges per protein. In general, beta-bulges produce two main changes in the structure of a beta-sheet: (1) disrupt the normal alternation of side-chain direction; (2) accentuate the twist of the sheet, altering the direction of the surrounding strands. PMID:8251933

  19. Thermal denaturation of beta-galactosidase and of two site-specific mutants.

    PubMed

    Edwards, R A; Jacobson, A L; Huber, R E

    1990-12-11

    The thermal denaturation of wild-type beta-galactosidase and two beta-galactosidases with substitutions at the active site was studied by kinetics, differential scanning calorimetry, electrophoresis, molecular exclusion chromatography, and circular dichroism. From the results, a model is developed for thermal denaturation of beta-galactosidase which includes the reversible dissociation of ligands, reversible formation of an inactive tetramer, irreversible dissociation of the inactive tetramer to inactive monomers, and subsequent aggregation of inactive monomers to dimers and larger aggregates. Under some conditions, partial reversibility of the activity loss could be demonstrated, and several intermediates in the thermal denaturation process were trapped by quenching and observed by electrophoresis and molecular exclusion chromatography. The ligands Mg2+ and phenylethyl thio-beta-D-galactoside increase the stability of beta-galactosidase to heat denaturation by shifting the ligand binding equilibrium according to Le Chatelier's principle, thus decreasing the concentration of the ligand-free tetramer which can proceed to subsequent steps. Circular dichroism results indicated that beta-galactosidase is dominated by beta-sheet with lower amounts of alpha-helix. Large changes in secondary structure begin to occur only after activity has been lost. Single amino acid changes at the active site can have significant effects on thermal stability of beta-galactosidases. Some of the effects result from increased thermal stability of the ligand-free enzyme itself. Other effects result from changes in ligand binding, but the magnitude of the resulting changes in stability is not related to the strength of ligand binding in a simple fashion. PMID:2125499

  20. Two-Dimensional Infrared (2DIR) Spectroscopy of the Peptide Beta3s Folding

    PubMed Central

    Lai, Zaizhi; Preketes, Nicholas K; Jiang, Jun; Mukamel, Shaul; Wang, Jin

    2013-01-01

    Probing underlying free energy landscape, pathways, and mechanism is the key for understanding protein folding in theory and experiment. Recently time-resolved two-dimensional infrared (2DIR) with femtosecond laser pulses, has emerged as a promising tool for investigating the protein folding dynamics on faster timescales than possible by NMR. We have employed molecular dynamics simulations to compute 2DIR spectra of the folding process of a peptide, Beta3s. Simulated non-chiral and chiral 2DIR signals illustrate the variation of the spectra as the peptide conformation evolves along the free energy landscape. Chiral spectra show stronger changes than the non-chiral signals because cross peaks caused by the formation of the β-sheet are clearly resolved. Chirality-induced 2DIR may be used to detect the folding of β-sheet proteins with high spectral and temporal resolution. PMID:23956818

  1. Synthetic peptide homologous to beta protein from Alzheimer disease forms amyloid-like fibrils in vitro.

    PubMed Central

    Kirschner, D A; Inouye, H; Duffy, L K; Sinclair, A; Lind, M; Selkoe, D J

    1987-01-01

    Progressive amyloid deposition in senile plaques and cortical blood vessels may play a central role in the pathogenesis of Alzheimer disease. We have used x-ray diffraction and electron microscopy to study the molecular organization and morphology of macromolecular assemblies formed by three synthetic peptides homologous to beta protein of brain amyloid: beta-(1-28), residues 1-28 of the beta protein; [Ala16]beta-(1-28), beta-(1-28) with alanine substituted for lysine at position 16; and beta-(18-28), residues 18-28 of the beta protein. beta-(1-28) readily formed fibrils in vitro that were similar in ultrastructure to the in vivo amyloid and aggregated into large bundles resembling those of senile plaque cores. X-ray patterns from partially dried, oriented pellets showed a cross-beta-conformation. A series of small-angle, equatorial maxima were consistent with a tubular fibril having a mean diameter of 86 A and a wall composed of pairs of cross-beta-pleated sheets. The data may also be consistent with pairs of cross-beta-sheets that are centered 71-A apart. [Ala16]beta-(1-28) formed beta-pleated sheet assemblies that were dissimilar to in vivo fibrils. The width of the 10-A spacing indicated stacks of about six sheets. Thus, substitution of the uncharged alanine for the positively charged lysine in the beta-strand region enhances the packing of the sheets and dramatically alters the type of macromolecular aggregate formed. beta-(18-28) formed assemblies that had even a greater number of stacked sheets, approximately equal to 24 per diffracting domain as indicated by the sharp intersheet reflection. Our findings on these homologous synthetic assemblies help to define the specific sequence that is required to form Alzheimer-type amyloid fibrils, thus providing an in vitro model of age-related cerebral amyloidogenesis. Images PMID:3477820

  2. Effect of peracylation of beta-cyclodextrin on the molecular structure and on the formation of inclusion complexes: an X-ray study.

    PubMed

    Añibarro, M; Gessler, K; Usón, I; Sheldrick, G M; Harata, K; Uekama, K; Hirayama, F; Abe, Y; Saenger, W

    2001-12-01

    The molecular structures of peracylated beta-cyclodextrins (CDs)--heptakis(2,3,6-tri-O-acetyl)-beta-CD (TA), heptakis(2,3,6-tri-O-propanoyl)-beta-CD (TP), and heptakis(2,3,6-tri-O-butanoyl)-beta-CD (TB)--have been determined by single crystal X-ray structure analysis. Due to the lack of O2...O3' hydrogen bonds between adjacent glucose units of the peracylated CDs, the macrocycles are elliptically distorted into nonplanar boat-shaped structures. The glucose units are tilted with respect to the O4 plane to relieve steric hindrance between adjacent acyl chains. In TB, all glucose units adopt the common (4)C(1)-chair conformation and one butanoyl chain intramolecularly penetrates the cavity, whereas, in TA and TP, one glucose unit each occurs in (O)S(2)-skew-boat conformation and one acyl chain closes the O6 side like a lid. In each of the three homologous molecules the intramolecular self-inclusion and lidlike orientation of acyl chains forces the associated O5-C5-C6-O6 torsion angle into a trans-conformation never observed before for unsubstituted CD; the inclusion behavior of TA, TP, and TB in solution has been studied by circular dichroism spectroscopy with the drug molsidomine and several organic compounds. No inclusion complexes are formed, which is attributed to the intramolecular closure of the molecular cavity by one of the acyl chains.

  3. Gender-related effects of 17-{beta}-estradiol and B-hexachlorocyclohexane on liver tumor formation in medaka (Oryzias latipes)

    SciTech Connect

    Cooke, J.B.; Hinton, D.E.

    1994-12-31

    When medaka were acutely exposed to diethylnitrosamine (DEN), greater incidence of hepatocarcinoma was seen in female versus male fish. This is possibly related to elevated female endogenous estrogens, which increase liver weight and production of vitellogenin. To examine roles of estrogens in tumor modulation, 21-day old medaka were exposed to DEN (200 ppm for 24 hr.), then fed purified diets containing the estrogenic compound {beta}-hexachlorocyclohexane ({beta}-HCH) or 17-{beta}estradiol (E2) for 6 months. Incidences of basophilic preneoplastic foci of cellular alteration in females receiving DEN and 0.01, 0.1, or 1.0 ppm E2 were three times the incidences in similarly-treated males. Also, incidences of basophilic foci in DEN + 0.1 ppm E2 males were significantly increased over DEN-only males and were equal to incidences in DEN-only females. Liver weights and hepatosomatic indices of males given 0.1 ppm E2 were not significantly different than females fed control diet. Females fed 0.01-10.0 ppm {beta}-HCH after DEN had 4--5 times greater incidences of basophilic foci as males. Gender-related effects on kinetics of growth rates and volumes of foci are being examined.

  4. Structural Biology Fact Sheet

    MedlinePlus

    ... Home > Science Education > Structural Biology Fact Sheet Structural Biology Fact Sheet Tagline (Optional) Middle/Main Content Area What is structural biology? Structural biology is a field of science focused ...

  5. Zika Virus Fact Sheet

    MedlinePlus

    ... 2014 Fact sheets Features Commentaries 2014 Multimedia Contacts Zika virus Fact sheet Updated 6 September 2016 Key facts ... and last for 2-7 days. Complications of Zika virus disease After a comprehensive review of evidence, there ...

  6. Minimalist design of water-soluble cross-[beta] architecture

    SciTech Connect

    Biancalana, Matthew; Makabe, Koki; Koide, Shohei

    2010-08-13

    Demonstrated successes of protein design and engineering suggest significant potential to produce diverse protein architectures and assemblies beyond those found in nature. Here, we describe a new class of synthetic protein architecture through the successful design and atomic structures of water-soluble cross-{beta} proteins. The cross-{beta} motif is formed from the lamination of successive {beta}-sheet layers, and it is abundantly observed in the core of insoluble amyloid fibrils associated with protein-misfolding diseases. Despite its prominence, cross-{beta} has been designed only in the context of insoluble aggregates of peptides or proteins. Cross-{beta}'s recalcitrance to protein engineering and conspicuous absence among the known atomic structures of natural proteins thus makes it a challenging target for design in a water-soluble form. Through comparative analysis of the cross-{beta} structures of fibril-forming peptides, we identified rows of hydrophobic residues ('ladders') running across {beta}-strands of each {beta}-sheet layer as a minimal component of the cross-{beta} motif. Grafting a single ladder of hydrophobic residues designed from the Alzheimer's amyloid-{beta} peptide onto a large {beta}-sheet protein formed a dimeric protein with a cross-{beta} architecture that remained water-soluble, as revealed by solution analysis and x-ray crystal structures. These results demonstrate that the cross-{beta} motif is a stable architecture in water-soluble polypeptides and can be readily designed. Our results provide a new route for accessing the cross-{beta} structure and expanding the scope of protein design.

  7. MHD Ballooning Instability in the Plasma Sheet

    SciTech Connect

    C.Z. Cheng; S. Zaharia

    2003-10-20

    Based on the ideal-MHD model the stability of ballooning modes is investigated by employing realistic 3D magnetospheric equilibria, in particular for the substorm growth phase. Previous MHD ballooning stability calculations making use of approximations on the plasma compressibility can give rise to erroneous conclusions. Our results show that without making approximations on the plasma compressibility the MHD ballooning modes are unstable for the entire plasma sheet where beta (sub)eq is greater than or equal to 1, and the most unstable modes are located in the strong cross-tail current sheet region in the near-Earth plasma sheet, which maps to the initial brightening location of the breakup arc in the ionosphere. However, the MHD beq threshold is too low in comparison with observations by AMPTE/CCE at X = -(8 - 9)R(sub)E, which show that a low-frequency instability is excited only when beq increases over 50. The difficulty is mitigated by considering the kinetic effects of ion gyrorad ii and trapped electron dynamics, which can greatly increase the stabilizing effects of field line tension and thus enhance the beta(sub)eq threshold [Cheng and Lui, 1998]. The consequence is to reduce the equatorial region of the unstable ballooning modes to the strong cross-tail current sheet region where the free energy associated with the plasma pressure gradient and magnetic field curvature is maximum.

  8. Regulatory roles of tumor necrosis factor-alpha and interleukin-1 beta in monocyte chemoattractant protein-1-mediated pulmonary granuloma formation in the rat.

    PubMed Central

    Flory, C. M.; Jones, M. L.; Miller, B. F.; Warren, J. S.

    1995-01-01

    Intravenous infusion of particulate yeast cell wall glucan into rats results in the synchronous development of angiocentric pulmonary granulomas that are composed almost entirely of monocytes and macrophages. Previous studies indicate that locally produced monocyte chemoattractant protein-1 (MCP-1) is required for full granuloma development. Because tumor necrosis factor-alpha (TNF-alpha) and interleukin 1 (IL-1) can induce MCP-1 production in a variety of cell types, we sought to determine their potential regulatory roles in this model. A single infusion of anti-TNF-alpha antibody at the time of glucan infusion (time 0) markedly reduced MCP-1 mRNA levels at 1 and 6 hours but not at later time points; there was no effect on granuloma size or number measured at 48 hours. When multiple infusions of anti-TNF-alpha antibody were administered over a 23-hour period (0 to 23 hours), MCP-1 mRNA was reduced through 24 hours, there was a significant reduction in peak bronchoalveolar lavage fluid MCP-1 activity at 48 hours, and there were marked reductions in granuloma size and number at 48 hours. Similar results were observed in animals that received infusions of anti-IL-1 beta. Infusion of anti-IL-1 beta at time 0 resulted in moderate reductions in MCP-1 mRNA at 1 and 6 hours and had no effect on granuloma size or number measured at 48 hours. When multiple infusions of anti-IL-1 beta were administered over a 23-hour period (0 to 23 hours), MCP-1 mRNA was reduced through 24 hours, there was a moderate reduction in peak bronchoalveolar lavage fluid MCP-1 activity at 48 hours, and there were marked reductions in granuloma size and number at 48 hours. A single infusion of anti-TNF-alpha and anti-IL-1 beta together at time 0 resulted in marked reductions in whole lung MCP-1 and mRNA at 1 and 6 hours, but not at 24 hours. Multiple combined infusions of anti-TNF-alpha and anti-IL-1 beta over a 23-hour period resulted in additive reductions in MCP-1 mRNA through 24 hours

  9. Determination of isoprene and alpha-/beta-pinene oxidation products in boreal forest aerosols from Hyytiälä, Finland: diel variations and possible link with particle formation events.

    PubMed

    Kourtchev, I; Ruuskanen, T M; Keronen, P; Sogacheva, L; Dal Maso, M; Reissell, A; Chi, X; Vermeylen, R; Kulmala, M; Maenhaut, W; Claeys, M

    2008-01-01

    Biogenic volatile organic compounds (VOCs), such as isoprene and alpha-/beta-pinene, are photo-oxidized in the atmosphere to non-volatile species resulting in secondary organic aerosol (SOA). The goal of this study was to examine time trends and diel variations of oxidation products of isoprene and alpha-/beta-pinene in order to investigate whether they are linked with meteorological parameters or trace gases. Separate day-night aerosol samples (PM(1)) were collected in a Scots pine dominated forest in southern Finland during 28 July-11 August 2005 and analyzed with gas chromatography/mass spectrometry (GC/MS). In addition, inorganic trace gases (SO(2), CO, NO(x), and O(3)), meteorological parameters, and the particle number concentration were monitored. The median total concentration of terpenoic acids (i.e., pinic acid, norpinic acid, and two novel compounds, 3-hydroxyglutaric acid and 2-hydroxy-4-isopropyladipic acid) was 65 ng m(-3), while that of isoprene oxidation products (i.e., 2-methyltetrols and C(5) alkene triols) was 17.2 ng m(-3). The 2-methyltetrols exhibited day/night variations with maxima during day-time, while alpha-/beta-pinene oxidation products did not show any diel variation. The sampling period was marked by a relatively high condensation sink, caused by pre-existing aerosol particles, and no nucleation events. In general, the concentration trends of the SOA compounds reflected those of the inorganic trace gases, meteorological parameters, and condensation sink. Both the isoprene and alpha-/beta-pinene SOA products were strongly influenced by SO(2), which is consistent with earlier reports that acidity plays a role in SOA formation. The results support previous proposals that oxygenated VOCs contribute to particle growth processes above boreal forest.

  10. Formation of gamma'-Ni3Al via the Peritectoid Reaction: gamma plus beta (+Al2O3) equals gamma'(+Al2O3)

    NASA Technical Reports Server (NTRS)

    Copland, Evan

    2008-01-01

    The activities of Al and Ni were measured using multi-cell Knudsen effusion-cell mass spectrometry (multi-cell KEMS), over the composition range 8 - 32 at.%Al and temperature range T = 1400 - 1750 K in the Ni-Al-O system. These measurements establish that equilibrium solidification of gamma'-Ni3Al-containing alloys occurs by the eutectic reaction, L (+ Al2O3) = gamma + beta (+ Al2O3), at 1640 plus or minus 1 K and a liquid composition of 24.8 plus or minus 0.2 at.%Al (at an unknown oxygen content). The {gamma + beta + Al2O3} phase field is stable over the temperature range 1633 - 1640 K, and gamma'-Ni3Al forms via the peritectiod, gamma + beta (+ Al2O3) = gamma'(+ Al2O3), at 1633 plus or minus 1 K. This behavior is inconsistent with the current Ni-Al phase diagram and a new diagram is proposed. This new Ni-Al phase diagram explains a number of unusual steady state solidification structures reported previously and provides a much simpler reaction scheme in the vicinity of the gamma'-Ni3Al phase field.

  11. Formation of gamma(sup prime)-Ni3Al via the Peritectoid Reaction: gamma + beta (+ Al2O3)=gamma(sup prime)(+ Al2O3)

    NASA Technical Reports Server (NTRS)

    Copeland, Evan

    2008-01-01

    The activities of Al and Ni were measured using multi-cell Knudsen effusion-cell mass spectrometry (multi-cell KEMS), over the composition range 8-32 at.%Al and temperature range T=1400-1750 K in the Ni-Al-O system. These measurements establish that equilibrium solidification of gamma(sup prime)-Ni3Al-containing alloys occurs by the eutectic reaction, L (+ Al2O3)=gamma + Beta(+ Al2O3), at 1640 +/- 1 K and a liquid composition of 24.8 +/- 0.2 at.%al (at an unknown oxygen content). The {gamma + Beta (+Al2O3} phase field is stable over the temperature range 1633-1640 K, and gamma(sup prime)-Ni3Al forms via the peritectoid, gamma + Beta (+ Al2O3)=gamma(sup prime) (+ Al2O3), at 1633 +/- 1 K. This behavior is consistent with the current Ni-Al phase diagram and a new diagram is proposed. This new Ni-Al phase diagram explains a number of unusual steady-state solidification structures reported previously and provides a much simpler reaction scheme in the vicinity of the gamma(sup prime)-Ni2Al phase field.

  12. Polyalanine and Abeta Aggregation Kinetics: Probing Intermediate Oligomer Formation and Structure Using Computer Simulations

    NASA Astrophysics Data System (ADS)

    Phelps, Erin Melissa

    2011-12-01

    The aggregation of proteins into stable, well-ordered structures known as amyloid fibrils has been associated with many neurodegenerative diseases. Amyloid fibrils are long straight, and un-branched structures containing several proto-filaments, each of which exhibits "cross beta structure," -- ribbon-like layers of large beta sheets whose strands run perpendicular to the fibril axis. It has been suggested in the literature that the pathway to fibril formation has the following steps: unfolded monomers associate into transient unstable oligomers, the oligomers undergo a rearrangement into the cross-beta structure and form into proto-filaments, these proto-filaments then associate and grow into fully formed fibrils. Recent experimental studies have determined that the unstable intermediate structures are toxic to cells and that their presence may play a key role in the pathogenesis of the amyloid diseases. Many efforts have been made to determine the structure of intermediate oligomer aggregates that form during the fibrillization process. The goal of this work is to provide details about the structure and formation kinetics of the unstable oligomers that appear in the fibril formation pathway. The specific aims of this work are to determine the steps in the fibril formation pathway and how the kinetics of fibrillization changes with variations in temperature and concentration. The method used is the application of discontinuous molecular dynamics to large systems of peptides represented with an intermediate resolution model, PRIME, that was previously developed in our group. Three different peptide sequences are simulated: polyalanine (KA14K), Abeta17-40, and Abeta17-42; the latter two are truncated sequences of the Alzheimer's peptide. We simulate the spontaneous assembly of these peptide chains from a random initial configuration of random coils. We investigate aggregation kinetics and oligomer formation of a system of 192 polyalanine (KA14K) chains over a

  13. Superfund fact sheet: Benzene. Fact sheet

    SciTech Connect

    Not Available

    1992-09-01

    The fact sheet describes benzene, a chemical that can be found in a variety of products, including petroleum products (e.g. gasoline), some household cleaners, and some glues and adhesives. Explanations of how people are exposed to benzene and how benzene can enter the body and may affect human health are given. The fact sheet is one in a series providing reference information about Superfund issues and is intended for readers with no formal scientific training.

  14. The iA{beta}5p {beta}-breaker peptide regulates the A{beta}(25-35) interaction with lipid bilayers through a cholesterol-mediated mechanism

    SciTech Connect

    Vitiello, Giuseppe; Grimaldi, Manuela; D'Ursi, Anna Maria; D'Errico, Gerardino

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer iA{beta}5p shows a significant tendency to deeply penetrates the hydrophobic core of lipid membrane. Black-Right-Pointing-Pointer A{beta}(25-35) locates in the external region of the membrane causing a re-positioning of CHOL. Black-Right-Pointing-Pointer iA{beta}5p withholds cholesterol in the inner hydrophobic core of the lipid membrane. Black-Right-Pointing-Pointer iA{beta}5p prevents the A{beta}(25-35) release from the lipid membrane. -- Abstract: Alzheimer's disease is characterized by the deposition of aggregates of the {beta}-amyloid peptide (A{beta}) in the brain. A potential therapeutic strategy for Alzheimer's disease is the use of synthetic {beta}-sheet breaker peptides, which are capable of binding A{beta} but unable to become part of a {beta}-sheet structure, thus inhibiting the peptide aggregation. Many studies suggest that membranes play a key role in the A{beta} aggregation; consequently, it is strategic to investigate the interplay between {beta}-sheet breaker peptides and A{beta} in the presence of lipid bilayers. In this work, we focused on the effect of the {beta}-sheet breaker peptide acetyl-LPFFD-amide, iA{beta}5p, on the interaction of the A{beta}(25-35) fragment with lipid membranes, studied by Electron Spin Resonance spectroscopy, using spin-labeled membrane components (either phospholipids or cholesterol). The ESR results show that iA{beta}5p influences the A{beta}(25-35) interaction with the bilayer through a cholesterol-mediated mechanism: iA{beta}5p withholds cholesterol in the inner hydrophobic core of the bilayer, making the interfacial region more fluid and capable to accommodate A{beta}(25-35). As a consequence, iA{beta}5p prevents the A{beta}(25-35) release from the lipid membrane, which is the first step of the {beta}-amyloid aggregation process.

  15. Silver ion high pressure liquid chromatography provides unprecedented separation of sterols: application to the enzymatic formation of cholesta-5,8-dien-3 beta-ol.

    PubMed Central

    Ruan, B; Shey, J; Gerst, N; Wilson, W K; Schroepfer, G J

    1996-01-01

    We report that silver ion HPLC provides remarkable separations of C27 sterols differing only in the number or location of olefinic double bonds. This technique has been extended to LC-MS, analysis of purified components by GC, GC-MS, and 1H NMR, and to its use on a semipreparative scale. The application of this methodology for the demonstration of the catalysis, by rat liver microsomes, of the conversion of 7-dehydrocholesterol to cholesta-5,8-dien-3 beta-ol is also presented. PMID:8876182

  16. Effect of Plasma Irradiation on Formation of TiO2 Thin-Film in Electron Cyclotron Resonance Sheet Plasma Source

    NASA Astrophysics Data System (ADS)

    Sugihara, Shinji; Ishii, Shigeyuki; Honbo, Eiji; Kato, Yushi

    2000-10-01

    We have studied the effect of plasma irradiation on formation of TiO2 thin-films. Substrates of deposition are irradiated by high-purity plasma of the electron cyclotron resonance (ECR) source. TiO2 thin-films are formed by reactive sputtering deposition. In the plasma source, divergent magnetic fields are formed with external permanent magnets whose N poles face each other. Microwave of 2.45-GHz frequency is launched through a quartz window from a slot antenna in-between the magnets. The generated plasma flows to side walls along the divergent magnetic fields. On one side a Ti target is placed and on the other a glass substrate is placed. The target form is a rectangle and the substrate is placed at a distance of 15 cm. A shutter is placed in front of the substrate to prevent plasma flowing from the resonance zone. Argon and oxygen gases are used for reactive sputtering and the working pressure is about 0.01 - 0.1 Pa. The negative dc bias of 1000 V is applied to the target for sputtering. The generated films are of rutile with shutter opened and of anatase with shutter closed. We will try to clear whether the effect is due to annealing or others.

  17. W-Band Sheet Beam Klystron Design

    SciTech Connect

    Scheitrum, G.; Caryotakis, G.; Burke, A.; Jensen, A.; Jongewaard, E.a Krasnykh, A.; Neubauer, M.; Phillips, R.; Rauenbuehler, K.; /SLAC

    2011-11-11

    Sheet beam devices provide important advantages for very high power, narrow bandwidth RF sources like accelerator klystrons [1]. Reduced current density and increased surface area result in increased power capabi1ity, reduced magnetic fields for focusing and reduced cathode loading. These advantages are offset by increased complexity, beam formation and transport issues and potential for mode competition in the ovennoded cavities and drift tube. This paper will describe the design issues encountered in developing a 100 kW peak and 2 kW average power sheet beam k1ystron at W-band including beam formation, beam transport, circuit design, circuit fabrication and mode competition.

  18. Perforating Thin Metal Sheets

    NASA Technical Reports Server (NTRS)

    Davidson, M. E.

    1985-01-01

    Sheets only few mils thick bonded together, punched, then debonded. Three-step process yields perforated sheets of metal. (1): Individual sheets bonded together to form laminate. (2): laminate perforated in desired geometric pattern. (3): After baking, laminate separates into individual sheets. Developed for fabricating conductive layer on blankets that collect and remove ions; however, perforated foils have other applications - as conductive surfaces on insulating materials; stiffeners and conductors in plastic laminates; reflectors in antenna dishes; supports for thermal blankets; lightweight grille cover materials; and material for mockup of components.

  19. Beta Blockers

    PubMed Central

    Admani, Shehla; Feldstein, Stephanie; Gonzalez, Ernesto M.

    2014-01-01

    Infantile hemangiomas are benign vascular tumors seen in 4.5 percent of neonates and infants. While most infantile hemangiomas can be managed with active nonintervention, a subset of patients will require more aggressive management. Here the authors review the use of beta-blockers in the treatment of infantile hemangiomas, including oral, topical, and multimodal treatment options. They discuss the latest data on propranolol, including criteria for patient selection, dosing recommendations, and appropriate monitoring for side effects and efficacy. Lastly, they review indications for topical timolol treatment and the potential benefits of concomitant laser therapy. PMID:25053982

  20. Relevance of organic farming and effect of climatological conditions on the formation of alpha-acids, beta-acids, desmethylxanthohumol, and xanthohumol in hop (Humulus lupulus L.).

    PubMed

    Keukeleire, Jelle De; Janssens, Ina; Heyerick, Arne; Ghekiere, Greet; Cambie, Joris; Roldan-Ruiz, Isabel; Bockstaele, Erik Van; Keukeleire, Denis De

    2007-01-10

    The concentrations of alpha-acids, beta-acids, desmethylxanthohumol, and xanthohumol were monitored in the hop varieties Admiral (A), Wye Challenger (WC), and First Gold (FG) during the harvest seasons of 2003 through 2005. Hops grown under an organic regimen were compared to plants grown conventionally in hop fields in close vicinity. The concentrations of the key compounds depended very much on climatological conditions showing, in general, highest levels in poorest weather conditions (2004). Of the three varieties studied, FG was the only one showing a clear trend for higher concentrations of secondary metabolites under organic growing conditions than under conventional farming conditions. Cultivation of A and WC seems to be very sensitive to climatic conditions and environmental stresses caused by pests and diseases, thereby leading to various results. WC proved to be a rich source of bioactive chalcones, particularly desmethylxanthohumol. PMID:17199314

  1. Formation of decarboxylated betacyanins in heated purified betacyanin fractions from red beet root (Beta vulgaris L.) monitored by LC-MS/MS.

    PubMed

    Wybraniec, Sławomir

    2005-05-01

    Mixtures of mono-, bi-, and tridecarboxylated betacyanins together with their corresponding neobetacyanins obtained from Beta vulgaris L. root juice as heating degradation products of betacyanins were identified by high-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS) and diode-array (LC-DAD) detection. Two monodecarboxy-betacyanin pairs of diastereomers were detected after the decarboxylation in ethanolic and aqueous solutions. Generation of 17-decarboxy-betacyanins and 2-decarboxy-betacyanins was suggested, the latter so far never having been attributed to betacyanin thermal degradation products. Other main products of decarboxylation were 2,17-bidecarboxybetanin, its isoform, and 14,15-dehydrogenated (neobetacyanin) derivatives of all the decarboxylated betacyanins. The results of this research are crucial in determining betacyanin degradation mechanisms in juices or extracts of B. vulgaris L. roots and other products containing these pigments.

  2. Inhibitory effects of 1,2,3,4,6-penta-O-galloyl-beta-D-glucopyranose on biofilm formation by Staphylococcus aureus.

    PubMed

    Lin, Mei-Hui; Chang, Fang-Rong; Hua, Mu-Yi; Wu, Yang-Chang; Liu, Shih-Tung

    2011-03-01

    1,2,3,4,6-Penta-O-galloyl-β-D-glucopyranose (PGG) is an active ingredient in plants that are commonly used in Chinese medicine to treat inflammation. We demonstrate here that PGG, at 6.25 μM, does not inhibit the growth of Staphylococcus aureus, and yet it prevents biofilm formation on polystyrene and polycarbonate surfaces. At the same concentration, PGG is not toxic to human epithelial and fibroblast cells. PGG has an IB₅₀ value, i.e., the PGG concentration that inhibits 50% biofilm formation, of 3.6 μM. The value is substantially lower than that of N-acetylcysteine, iodoacetamide, and N-phenyl maleimide, which are known to inhibit biofilm formation by S. aureus. Biochemical and scanning electron microscopy results also reveal that PGG inhibits initial attachment of the bacteria to solid surface and the synthesis of polysaccharide intercellular adhesin, explaining how PGG inhibits biofilm formation. The results of this study demonstrate that coating PGG on polystyrene and silicon rubber surfaces with polyaniline prevents biofilm formation, indicating that PGG is highly promising for clinical use in preventing biofilm formation by S. aureus.

  3. Formation of fast shocks by magnetic reconnection in the solar corona

    SciTech Connect

    Hsieh, M. H.; Tsai, C. L.; Ma, Z. W.; Lee, L. C.

    2009-09-15

    Reconnections of magnetic fields over the solar surface are expected to generate abundant magnetohydrodynamic (MHD) discontinuities and shocks, including slow shocks and rotational discontinuities. However, the generation of fast shocks by magnetic reconnection process is relatively not well studied. In this paper, magnetic reconnection in a current sheet is studied based on two-dimensional resistive MHD numerical simulations. Magnetic reconnections in the current sheet lead to the formation of plasma jets and plasma bulges. It is further found that the plasma bulges, the leading part of plasma jets, in turn lead to the generation of fast shocks on flanks of the bulges. The simulation results show that during the magnetic reconnection process, the plasma forms a series of structures: plasma jets, plasma bulges, and fast shocks. As time increases, the bulges spread out along the current sheet ({+-}z direction) and the fast shocks move just ahead of the bulges. The effects of initial parameters {rho}{sub s}/{rho}{sub m}, {beta}{sub {infinity}}, and t{sub rec} on the fast shock generation are also examined, where {rho}{sub s}/{rho}{sub m} is the ratio of plasma densities on two sides of the initial current sheet, {beta}{sub {infinity}}=P{sub {infinity}}/(B{sub {infinity}}{sup 2}/2{mu}{sub 0}), P{sub {infinity}} is the plasma pressure and B{sub {infinity}} is the magnetic field magnitude far from the current sheet, and t{sub rec} is the reconnection duration. In the asymmetric case with {rho}{sub s}/{rho}{sub m}=2, {beta}{sub {infinity}}=0.01 and t{sub rec}=1000, the maximum Alfven Mach number of fast shocks (M{sub A1max}) is M{sub A1max} congruent with 1.1, where M{sub A1}=V{sub n1}/V{sub A1}, and V{sub n1} and V{sub A1} are, respectively, the normal upstream fluid velocity and the upstream Alfven speed in the fast shocks frame. As the density ratio {rho}{sub s}/{rho}{sub m} (=1-8) and plasma beta {beta}{sub {infinity}} (=0.0001-1) increase, M{sub A1max} varies

  4. Fiber formation of a synthetic spider peptide derived from Nephila clavata.

    PubMed

    Hidaka, Yuji; Kontani, Ko-Ichi; Taniguchi, Rina; Saiki, Masatoshi; Yokoi, Sayoko; Yukuhiro, Kenji; Yamaguchi, Hiroshi; Miyazawa, Mitsuhiro

    2011-01-01

    Dragline silk is a high-performance biopolymer with exceptional mechanical properties. Artificial spider dragline silk is currently prepared by a recombinant technique or chemical synthesis. However, the recombinant process is costly and large-sized synthetic peptides are needed for fiber formation. In addition, the silk fibers that are produced are much weaker than a fiber derived from a native spider. In this study, a small peptide was chemically synthesized and examined for its ability to participate in fiber formation. A short synthetic peptide derived from Nephila clavata was prepared by a solid-phase peptide method, based on a prediction using the hydrophobic parameter of each individual amino acid residue. After purification of the spider peptide, fiber formation was examined under several conditions. Fiber formation proceeded in the acidic pH range, and larger fibers were produced when organic solvents such as trifluoroethanol and acetonitrile were used at an acidic pH. Circular dichroism measurements of the spider peptide indicate that the peptide has a beta-sheet structure and that the formation of a beta-sheet structure is required for the spider peptide to undergo fiber formation. PMID:20564008

  5. Structure of beta-crystallite assemblies formed by Alzheimer beta-amyloid protein analogues: analysis by x-ray diffraction.

    PubMed Central

    Inouye, H.; Fraser, P. E.; Kirschner, D. A.

    1993-01-01

    To elucidate the relation between amyloid fibril formation in Alzheimer disease and the primary structure of the beta/A4 protein, which is the major component of the amyloid, we have been investigating the ability of peptides sharing sequences with beta/A4 to form fibrils in vitro. In previous studies we focused on the macroscopic morphology of the assemblies formed by synthetic peptides corresponding in sequence to different regions of this protein. In the present study we analyze the x-ray diffraction patterns obtained from these assemblies. All specimens showed wide angle reflections that could be indexed by an orthogonal lattice of beta-crystallites having unit cell dimensions a = 9.4 A, b = 7 A, and c = 10 A, where a refers to hydrogen bonding direction, b to polypeptide chain direction, and c to intersheet direction. Given the amino acid sequence of beta/A4 as NH2-DAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIAT-COOH, we found that, based on their orientation and assembly, the analogues could be classified into three groups: Group A, residues 19-28, 13-28, 12-28, 11-28, 9-28, 1-28, 1-38, 1-40, 6-25, 11-25 and 34-42; Group B, residues 18-28, 17-28, and 15-28; and Group C, residues 22-35 and 26-33. For Groups A and C, the sharpest reflections were (h00), indicating that the assemblies were fibrillar, i.e., elongated in a single direction. Lateral alignment of the crystallites in Group A account for its cross-beta pattern, in which the hydrogen bonding (H-bonding) direction is the fiber (rotation) axis. By comparison, the beta-crystallites of Group C had no preferential orientation, thus giving circular scattering. For Group B, the sharpest reflections were (h0l) on the meridian, indicating that the assemblies were plate-like, i.e., extended in two directions. A series of equatorial Bragg reflections having a 40 A period indicated regular stacking of the plates, and the rotation axis was normal to the surface of the plates. Of the Group A peptides, the analogues 11

  6. Developing Fact Sheets.

    ERIC Educational Resources Information Center

    Weiler, Robert M.

    1998-01-01

    Presents an assignment that allows preservice health educators to learn how to develop fact sheets for communicating health information. The process of developing fact sheets involves selecting a topic, selecting a target audience, researching the topic, writing the message, constructing the draft, and pretesting the product. Strategies for…

  7. Mechanics of Sheeting Joints

    NASA Astrophysics Data System (ADS)

    Martel, S. J.

    2015-12-01

    Physical breakdown of rock across a broad scale spectrum involves fracturing. In many areas large fractures develop near the topographic surface, with sheeting joints being among the most impressive. Sheeting joints share many geometric, textural, and kinematic features with other joints (opening-mode fractures) but differ in that they are (a) discernibly curved, (b) open near the topographic surface, and (c) form subparallel to the topographic surface. Where sheeting joints are geologically young, the surface-parallel compressive stresses are typically several MPa or greater. Sheeting joints are best developed beneath domes, ridges, and saddles; they also are reported, albeit rarely, beneath valleys or bowls. A mechanism that accounts for all these associations has been sought for more than a century: neither erosion of overburden nor high lateral compressive stresses alone suffices. Sheeting joints are not accounted for by Mohr-Coulomb shear failure criteria. Principles of linear elastic fracture mechanics, together with the mechanical effect of a curved topographic surface, do provide a basis for understanding sheeting joint growth and the pattern sheeting joints form. Compressive stresses parallel to a singly or doubly convex topographic surface induce a tensile stress perpendicular to the surface at shallow depths; in some cases this alone could overcome the weight of overburden to open sheeting joints. If regional horizontal compressive stresses, augmented by thermal stresses, are an order of magnitude or so greater than a characteristic vertical stress that scales with topographic amplitude, then topographic stress perturbations can cause sheeting joints to open near the top of a ridge. This topographic effect can be augmented by pressure within sheeting joints arising from water, ice, or salt. Water pressure could be particularly important in helping drive sheeting joints downslope beneath valleys. Once sheeting joints have formed, the rock sheets between

  8. Ellagic acid promotes A{beta}42 fibrillization and inhibits A{beta}42-induced neurotoxicity

    SciTech Connect

    Feng, Ying; Yang, Shi-gao; Du, Xue-ting; Zhang, Xi; Sun, Xiao-xia; Zhao, Min; Sun, Gui-yuan; Liu, Rui-tian

    2009-12-25

    Smaller, soluble oligomers of {beta}-amyloid (A{beta}) play a critical role in the pathogenesis of Alzheimer's disease (AD). Selective inhibition of A{beta} oligomer formation provides an optimum target for AD therapy. Some polyphenols have potent anti-amyloidogenic activities and protect against A{beta} neurotoxicity. Here, we tested the effects of ellagic acid (EA), a polyphenolic compound, on A{beta}42 aggregation and neurotoxicity in vitro. EA promoted A{beta} fibril formation and significant oligomer loss, contrary to previous results that polyphenols inhibited A{beta} aggregation. The results of transmission electron microscopy (TEM) and Western blot displayed more fibrils in A{beta}42 samples co-incubated with EA in earlier phases of aggregation. Consistent with the hypothesis that plaque formation may represent a protective mechanism in which the body sequesters toxic A{beta} aggregates to render them harmless, our MTT results showed that EA could significantly reduce A{beta}42-induced neurotoxicity toward SH-SY5Y cells. Taken together, our results suggest that EA, an active ingredient in many fruits and nuts, may have therapeutic potential in AD.

  9. Current status of liquid sheet radiator research

    NASA Technical Reports Server (NTRS)

    Chubb, Donald L.; Calfo, Frederick D.; Mcmaster, Matthew S.

    1993-01-01

    Initial research on the external flow, low mass liquid sheet radiator (LSR), has been concentrated on understanding its fluid mechanics. The surface tension forces acting at the edges of the sheet produce a triangular planform for the radiating surface of width, W, and length, L. It has been experimentally verified that (exp L)/W agrees with the theoretical result, L/W = (We/8)exp 1/2, where We is the Weber number. Instability can cause holes to form in regions of large curvature such as where the edge cylinders join the sheet of thickness, tau. The W/tau limit that will cause hole formation with subsequent destruction of the sheet has yet to be reached experimentally. Although experimental measurements of sheet emissivity have not yet been performed because of limited program scope, calculations of the emissivity and sheet lifetime is determined by evaporation losses were made for two silicon based oils; Dow Corning 705 and Me(sub 2). Emissivities greater than 0.75 are calculated for tau greater than or equal to 200 microns for both oils. Lifetimes for Me(sub 2) are much longer than lifetimes for 705. Therefore, Me(sub 2) is the more attractive working fluid for higher temperatures (T greater than or equal to 400 K).

  10. Emittance Measurements for a Thin Liquid Sheet Flow

    NASA Technical Reports Server (NTRS)

    Englehart, Amy N.; McConley, Marc W.; Chubb, Donald L.

    1996-01-01

    The Liquid Sheet Radiator (LSR) is an external flow radiator that uses a triangular-shaped flowing liquid sheet as the radiating surface. It has potentially much lower mass than solid wall radiators such as pumped loop and heat pipe radiators, along with being nearly immune to micrometeoroid penetration. The LSR has an added advantage of simplicity. Surface tension causes a thin (100-300 microns) liquid sheet to coalesce to a point, causing the sheet flow to have a triangular shape. Such a triangular sheet is desirable since it allows for simple collection of the flow at a single point. A major problem for all external flow radiators is the requirement that the working fluid be of very low (approx. 10(sup -8) torr) vapor pressure to keep evaporative losses low. As a result, working fluids are limited to certain oils (such as used in diffusion pumps) for low temperatures (300-400 K) and liquid metals for higher temperatures. Previous research on the LSR has been directed at understanding the fluid mechanics of thin sheet flows and assessing the stability of such flows, especially with regard to the formation of holes in the sheet. Taylor studied extensively the stability of thin liquid sheets both theoretically and experimentally. He showed that thin sheets in a vacuum are stable. The latest research has been directed at determining the emittance of thin sheet flows. The emittance was calculated from spectral transmittance data for the Dow Corning 705 silicone oil. By experimentally setting up a sheet flow, the emittance was also determined as a function of measurable quantities, most importantly, the temperature drop between the top of the sheet and the temperature at the coalescence point of the sheet. Temperature fluctuations upstream of the liquid sheet were a potential problem in the analysis and were investigated.

  11. Nuclear Data Sheets for A = 193

    SciTech Connect

    Achterberg, E.; Capurro, O.A.; Marti, G.V.; Vanin, V.R.; Castro, R.M.

    2006-01-15

    The present revision of the properties for the nuclides belonging to the A = 193 mass chain contains many improvements, corrections and additions to the material presented in previous evaluations (1998Ar07, Nucl. Data Sheets 83, 921 (1998); 1990Sh30, Nucl, Data Sheets 61, 519 (1990)). Among these are measurement results for quadrupole moments, angular distribution coefficients, half-lives and g-factors, for both previously known and new transitions and levels. In addition, major changes to the previously known status of this mass chain consist in the inclusion of data for new superdeformed bands in {sup 193}Pb, and the creation of level schemes for {sup 193}Bi, {sup 193}Po and {sup 193}At. The latter were previously unavailable, except for a very limited attempt in the case of {sup 193}Po, which was not confirmed in later work. Furthermore, the {sup 193}Os beta decay was re-evaluated in order to account for new absolute intensity measurements.

  12. The Arabidopsis P4-ATPase ALA3 localizes to the golgi and requires a beta-subunit to function in lipid translocation and secretory vesicle formation.

    PubMed

    Poulsen, Lisbeth Rosager; López-Marqués, Rosa Laura; McDowell, Stephen C; Okkeri, Juha; Licht, Dirk; Schulz, Alexander; Pomorski, Thomas; Harper, Jeffrey F; Palmgren, Michael Gjedde

    2008-03-01

    Vesicle budding in eukaryotes depends on the activity of lipid translocases (P(4)-ATPases) that have been implicated in generating lipid asymmetry between the two leaflets of the membrane and in inducing membrane curvature. We show that Aminophospholipid ATPase3 (ALA3), a member of the P(4)-ATPase subfamily in Arabidopsis thaliana, localizes to the Golgi apparatus and that mutations of ALA3 result in impaired growth of roots and shoots. The growth defect is accompanied by failure of the root cap to release border cells involved in the secretion of molecules required for efficient root interaction with the environment, and ala3 mutants are devoid of the characteristic trans-Golgi proliferation of slime vesicles containing polysaccharides and enzymes for secretion. In yeast complementation experiments, ALA3 function requires interaction with members of a novel family of plant membrane-bound proteins, ALIS1 to ALIS5 (for ALA-Interacting Subunit), and in this host ALA3 and ALIS1 show strong affinity for each other. In planta, ALIS1, like ALA3, localizes to Golgi-like structures and is expressed in root peripheral columella cells. We propose that the ALIS1 protein is a beta-subunit of ALA3 and that this protein complex forms an important part of the Golgi machinery required for secretory processes during plant development.

  13. Entacapone and tolcapone, two catechol O-methyltransferase inhibitors, block fibril formation of alpha-synuclein and beta-amyloid and protect against amyloid-induced toxicity.

    PubMed

    Di Giovanni, Saviana; Eleuteri, Simona; Paleologou, Katerina E; Yin, Guowei; Zweckstetter, Markus; Carrupt, Pierre-Alain; Lashuel, Hilal A

    2010-05-14

    Parkinson disease (PD) is the second most common neurodegenerative disorder after Alzheimer disease (AD). There is considerable consensus that the increased production and/or aggregation of alpha-synuclein (alpha-syn) plays a central role in the pathogenesis of PD and related synucleinopathies. Current therapeutic strategies for treating PD offer mainly transient symptomatic relief and aim at the restitution of dopamine levels to counterbalance the loss of dopaminergic neurons. Therefore, the identification and development of drug-like molecules that block alpha-synuclein aggregation and prevent the loss of dopaminergic neurons are desperately needed to treat or slow the progression of PD. Here, we show that entacapone and tolcapone are potent inhibitors of alpha-syn and beta-amyloid (Abeta) oligomerization and fibrillogenesis, and they also protect against extracellular toxicity induced by the aggregation of both proteins. Comparison of the anti-aggregation properties of entacapone and tolcapone with the effect of five other catechol-containing compounds, dopamine, pyrogallol, gallic acid, caffeic acid, and quercetin on the oligomerization and fibrillization of alpha-syn and Abeta, demonstrate that the catechol moiety is essential for the anti-amyloidogenic activity. Our findings present the first characterization of the anti-amyloidogenic properties of tolcapone and entacapone against both alpha-synuclein and Abeta42 and highlight the potential of this class of nitro-catechol compounds as anti-amyloidogenic agents. Their inhibitory properties, mode of action, and structural properties suggest that they constitute promising lead compounds for further optimization. PMID:20150427

  14. {alpha}- and {beta}-La{sub 4}Ti{sub 9}Si{sub 4}O{sub 30}. Synthesis and structure of the second member (m = 2) of novel layered oxosilicates containing (110) rutile sheets. Electrical property and band structure characterization of the mixed-valence titanium(III/IV) oxosilicate series, La{sub 4}Ti(Si{sub 2}O{sub 7}){sub 2}(TiO{sub 2}){sub 4m} (m = 1, 2)

    SciTech Connect

    Wang, S.; Hwu, S.J.; Paradis, J.A.; Whangbo, M.H.

    1995-05-24

    Detailed description is presented of molten salt synthesis, single crystal structures, and a comparison is offered of the {alpha}- and {beta}-La{sub 4}Ti{sub 9}Si{sub 4}O{sub 30} phases. The electrical property and band struture of this mixed-valence titanium (III/IV) oxosilicate series, La{sub 4}Ti(Si{sub 2}O{sub 7}){sub 2}(TiO{sub 2}){sub 4m} (m = 1,2), are discussed in terms of electronic interactions in a confined space with respect to the (110) rutile sheets. The results from the extended Hueckel tight binding calculations and the bond valence sum analysis are contrasted with regard to charge distribution. 33 refs., 9 figs., 3 tabs.

  15. Effects of increased anionic charge in the beta-globin chain on assembly of hemoglobin in vitro.

    PubMed

    Adachi, K; Yamaguchi, T; Pang, J; Surrey, S

    1998-02-15

    Studies on assembly in vitro of alpha-globin chains with recombinant beta16 Gly-->Asp, beta95 Lys-->Glu, beta120 Lys-->Glu and beta16 Gly-->Asp, 120 Lys-->Glu human beta-globin chain variants in addition to human betaA- and betaS-globin chains were performed to evaluate effects of increased anionic charge in the beta chain on hemoglobin assembly using soluble recombinant beta-globin chains expressed in bacteria. A beta112 Cys-->Asp change was also engineered to monitor effects on assembly of increased negative charge at alpha1beta1 interaction sites. Order of tetramer formation in vitro under limiting alpha-globin chain conditions showed Hb betaG16D, K120E = Hb betaK120E = Hb betaK95E > Hb betaG16D > Hb A > Hb S > Hb betaC112D. In addition, beta112 Cys-->Asp chains exist as monomers rather than beta4 tetramers in the absence of alpha chains, and the beta chain in Hb betaC112D tetramers was readily exchanged by addition of betas. These results suggest that affinity between alpha and beta chains is promoted by negatively-charged beta chains up to a maximum of two additional net negative charges and is independent of location on the surface except at the alpha1beta1 interaction site. In addition, our findings show that beta112 Cys on the G helix is critical for facilitating formation of stable alphabeta dimers, which then form functional hemoglobin tetramers, and that beta112 Cys-->Asp inhibits formation of stable alpha1beta1 and beta1beta2 interactions in alpha2beta2 and beta4 tetramers, respectively. PMID:9454775

  16. Interhemispheric ice-sheet synchronicity during the last glacial maximum

    USGS Publications Warehouse

    Weber, Michael E.; Clark, Peter U.; Ricken, Werner; Mitrovica, Jerry X.; Hostetler, Steven W.; Kuhn, Gerhard

    2011-01-01

    The timing of the last maximum extent of the Antarctic ice sheets relative to those in the Northern Hemisphere remains poorly understood. We develop a chronology for the Weddell Sea sector of the East Antarctic Ice Sheet that, combined with ages from other Antarctic ice-sheet sectors, indicates that the advance to and retreat from their maximum extent was within dating uncertainties synchronous with most sectors of Northern Hemisphere ice sheets. Surface climate forcing of Antarctic mass balance would probably cause an opposite response, whereby a warming climate would increase accumulation but not surface melting. Our new data support teleconnections involving sea-level forcing from Northern Hemisphere ice sheets and changes in North Atlantic deep-water formation and attendant heat flux to Antarctic grounding lines to synchronize the hemispheric ice sheets.

  17. In-situ Pb isotope analysis of Fe-Ni-Cu sulphides by laser ablation multi-collector ICPMS: New insights into ore formation in the Sudbury impact melt sheet

    NASA Astrophysics Data System (ADS)

    Darling, J. R.; Storey, C. D.; Hawkesworth, C. J.; Lightfoot, P. C.

    2012-12-01

    Laser-ablation (LA) multi-collector inductively coupled plasma mass spectrometry (MC-ICPMS) is ideally suited to in situ determination of isotope ratios in sulphide minerals. Using samples of magmatic sulphide ore from the Sudbury impact structure, we test LA-MC-ICPMS analytical protocols that aim to meet a range of analytical challenges in the analysis of Pb isotopes. These include: potential matrix sensitive isotopic fractionation; interferences on Pb isotopes; low melting points of many sulphide minerals; the availability of standards. Magmatic sulphides of wide ranging mineralogy (pyrrhotite, pentlandite, chalcopyrite, pyrite and sphalerite) were analysed for Pb isotopic composition, using the silicate glass NIST SRM 610 as an external standard to correct for instrumental mass-fractionation. Despite matrix sensitive melting and re-deposition around ablation pits, several lines of evidence indicate that all analyses are accurate, within typical analytical uncertainties of 0.003-2% (2σ), and that the defined approach is insensitive to compositional diversity in sample matrix: (a) laser ablation and dissolution based measurements of sulphide powders are in agreement; (b) analyses from each sample define isochron ages within uncertainty of the known crystallization age (1850 Ma); (c) the results of sulphide measurements by laser ablation are consistent with age-corrected feldspar analyses from the same samples. The results have important implications for ore formation in Sudbury. The Pb isotope data regressions are consistent with age corrected feldspar analyses from each respective sample, which together with time integrated Th/U ratios that match whole rock values (3.1, 4.0 and 6.1 for the Worthington, Copper Cliff and Parkin Offset Dykes, respectively) indicate chemical equilibrium between the silicate and sulphide systems during ore formation. The sulphides within each respective sample have indistinguishable model initial Pb isotope ratios (207Pb/204Pbm

  18. Microcomponent sheet architecture

    DOEpatents

    Wegeng, R.S.; Drost, M.K..; McDonald, C.E.

    1997-03-18

    The invention is a microcomponent sheet architecture wherein macroscale unit processes are performed by microscale components. The sheet architecture may be a single laminate with a plurality of separate microcomponent sections or the sheet architecture may be a plurality of laminates with one or more microcomponent sections on each laminate. Each microcomponent or plurality of like microcomponents perform at least one unit operation. A first laminate having a plurality of like first microcomponents is combined with at least a second laminate having a plurality of like second microcomponents thereby combining at least two unit operations to achieve a system operation. 14 figs.

  19. Microcomponent sheet architecture

    DOEpatents

    Wegeng, Robert S.; Drost, M. Kevin; McDonald, Carolyn E.

    1997-01-01

    The invention is a microcomponent sheet architecture wherein macroscale unit processes are performed by microscale components. The sheet architecture may be a single laminate with a plurality of separate microcomponent sections or the sheet architecture may be a plurality of laminates with one or more microcomponent sections on each laminate. Each microcomponent or plurality of like microcomponents perform at least one unit operation. A first laminate having a plurality of like first microcomponents is combined with at least a second laminate having a plurality of like second microcomponents thereby combining at least two unit operations to achieve a system operation.

  20. Individual variation in plasma estradiol-17beta and androgen levels during egg formation in the European starling Sturnus vulgaris: implications for regulation of yolk steroids.

    PubMed

    Williams, T D; Kitaysky, A S; Vézina, F

    2004-05-01

    While it is clear that maternal transfer of steroids to egg yolk can have significant effects on offspring phenotype, an unresolved question is whether females can facultatively adjust yolk hormone levels independently of their own plasma levels or whether yolk steroid levels are simply a direct consequence of temporal variation in the female's hormonal status. In part, this is because we lack detailed information about the day-to-day pattern of changes in plasma hormone levels during the laying cycle for non-domesticated birds. Here, we describe changes in plasma estradiol-17beta (E2) and androgens, throughout laying in relation to specific stages of ovarian follicular development in the European starling (Sturnus vulgaris). Plasma E2 levels increased rapidly from the onset of rapid yolk development (RYD) to reach maximum levels in birds with a complete follicle hierarchy (> or = 4 yolky follicles). However, levels decreased linearly throughout the later stages of follicle development returning to pre-breeding values before the final yolky follicle was ovulated. In females with > or = 4 yolky follicles there was 10-fold variation in plasma E2 levels among individual females, but this was not related to plasma levels of the main yolk precursor vitellogenin or to the total mass of yolky follicles developing at the time of blood sampling. In contrast to E2, plasma androgen levels showed only a very gradual linear decline throughout the laying cycle from pre-RYD to clutch completion. Furthermore, androgen levels showed less individual variability: 4-fold variation among females with > or = 4 yolky follicles, although this was also independent of our measures of reproductive function. Data on inter- and intra-individual variation in female hormone levels are important to set-up a priori predictions for, and interpretation of, studies of yolk hormone levels. PMID:15081834

  1. Polarised light sheet tomography.

    PubMed

    Reidt, Sascha L; O'Brien, Daniel J; Wood, Kenneth; MacDonald, Michael P

    2016-05-16

    The various benefits of light sheet microscopy have made it a widely used modality for capturing three-dimensional images. It is mostly used for fluorescence imaging, but recently another technique called light sheet tomography solely relying on scattering was presented. The method was successfully applied to imaging of plant roots in transparent soil, but is limited when it comes to more turbid samples. This study presents a polarised light sheet tomography system and its advantages when imaging in highly scattering turbid media. The experimental configuration is guided by Monte Carlo radiation transfer methods, which model the propagation of a polarised light sheet in the sample. Images of both reflecting and absorbing phantoms in a complex collagenous matrix were acquired, and the results for different polarisation configurations are compared. Focus scanning methods were then used to reduce noise and produce three-dimensional reconstructions of absorbing targets.

  2. Cerebral Aneurysms Fact Sheet

    MedlinePlus

    ... Awards Enhancing Diversity Find People About NINDS Cerebral Aneurysms Fact Sheet See a list of all NINDS ... I get more information? What is a cerebral aneurysm? A cerebral aneurysm (also known as an intracranial ...

  3. Global ice sheet modeling

    SciTech Connect

    Hughes, T.J.; Fastook, J.L.

    1994-05-01

    The University of Maine conducted this study for Pacific Northwest Laboratory (PNL) as part of a global climate modeling task for site characterization of the potential nuclear waste respository site at Yucca Mountain, NV. The purpose of the study was to develop a global ice sheet dynamics model that will forecast the three-dimensional configuration of global ice sheets for specific climate change scenarios. The objective of the third (final) year of the work was to produce ice sheet data for glaciation scenarios covering the next 100,000 years. This was accomplished using both the map-plane and flowband solutions of our time-dependent, finite-element gridpoint model. The theory and equations used to develop the ice sheet models are presented. Three future scenarios were simulated by the model and results are discussed.

  4. Avian Fact Sheet

    SciTech Connect

    NWCC Wildlife Work Group

    2004-12-01

    OAK-B135 After conducting four national research meetings, producing a document guiding research: Metrics and Methods for Determining or Monitoring Potential Impacts on Birds at Existing and Proposed Wind Energy Sites, 1999, and another paper, Avian Collisions with Wind Turbines: A Summary of Existing Studies and Comparisons to Other Sources of Avian Collision Mortality in the United States, 2001, the subcommittee recognized a need to summarize in a short fact sheet what is known about avian-wind interaction and what questions remain. This fact sheet attempts to summarize in lay terms the result of extensive discussion about avian-wind interaction on land. This fact sheet does not address research conducted on offshore development. This fact sheet is not intended as a conclusion on the subject; rather, it is a summary as of Fall/Winter 2002.

  5. Polarised light sheet tomography.

    PubMed

    Reidt, Sascha L; O'Brien, Daniel J; Wood, Kenneth; MacDonald, Michael P

    2016-05-16

    The various benefits of light sheet microscopy have made it a widely used modality for capturing three-dimensional images. It is mostly used for fluorescence imaging, but recently another technique called light sheet tomography solely relying on scattering was presented. The method was successfully applied to imaging of plant roots in transparent soil, but is limited when it comes to more turbid samples. This study presents a polarised light sheet tomography system and its advantages when imaging in highly scattering turbid media. The experimental configuration is guided by Monte Carlo radiation transfer methods, which model the propagation of a polarised light sheet in the sample. Images of both reflecting and absorbing phantoms in a complex collagenous matrix were acquired, and the results for different polarisation configurations are compared. Focus scanning methods were then used to reduce noise and produce three-dimensional reconstructions of absorbing targets. PMID:27409945

  6. Biodiesel Basics (Fact Sheet)

    SciTech Connect

    Not Available

    2014-06-01

    This fact sheet provides a brief introduction to biodiesel, including a discussion of biodiesel blends, which blends are best for which vehicles, where to buy biodiesel, how biodiesel compares to diesel fuel in terms of performance, how biodiesel performs in cold weather, whether biodiesel use will plug vehicle filters, how long-term biodiesel use may affect engines, biodiesel fuel standards, and whether biodiesel burns cleaner than diesel fuel. The fact sheet also dismisses the use of vegetable oil as a motor fuel.

  7. Energy information sheets

    SciTech Connect

    1995-07-01

    The National Energy Information Center (NEIC), as part of its mission, provides energy information and referral assistance to Federal, State, and local governments, the academic community, business and industrial organizations, and the public. The Energy Information Sheets was developed to provide general information on various aspects of fuel production, prices, consumption, and capability. Additional information on related subject matter can be found in other Energy Information Administration (EIA) publications as referenced at the end of each sheet.

  8. Transporter for Treated Sheet Materials

    NASA Technical Reports Server (NTRS)

    Pollack, M., H.

    1983-01-01

    Plastic spacers keep parts separated during transport or storage. Cart with rods and spacers holds sheets with delicate finishes for storage or transport. Sheets supported vertically by rods, or horizontally. Spacers keep sheets separated. Designed to eliminate time and expense of tapping, wrapping, and sometimes refinishing aluminum sheets with delicate anodized finished.

  9. Contact prediction for beta and alpha-beta proteins using integer linear optimization and its impact on the first principles 3D structure prediction method ASTRO-FOLD.

    PubMed

    Rajgaria, R; Wei, Y; Floudas, C A

    2010-06-01

    An integer linear optimization model is presented to predict residue contacts in beta, alpha + beta, and alpha/beta proteins. The total energy of a protein is expressed as sum of a C(alpha)-C(alpha) distance dependent contact energy contribution and a hydrophobic contribution. The model selects contact that assign lowest energy to the protein structure as satisfying a set of constraints that are included to enforce certain physically observed topological information. A new method based on hydrophobicity is proposed to find the beta-sheet alignments. These beta-sheet alignments are used as constraints for contacts between residues of beta-sheets. This model was tested on three independent protein test sets and CASP8 test proteins consisting of beta, alpha + beta, alpha/beta proteins and it was found to perform very well. The average accuracy of the predictions (separated by at least six residues) was approximately 61%. The average true positive and false positive distances were also calculated for each of the test sets and they are 7.58 A and 15.88 A, respectively. Residue contact prediction can be directly used to facilitate the protein tertiary structure prediction. This proposed residue contact prediction model is incorporated into the first principles protein tertiary structure prediction approach, ASTRO-FOLD. The effectiveness of the contact prediction model was further demonstrated by the improvement in the quality of the protein structure ensemble generated using the predicted residue contacts for a test set of 10 proteins.

  10. Creating supersecondary structures with BuildBeta.

    PubMed

    Crivelli, Silvia; Max, Nelson

    2013-01-01

    BuildBeta is a feature of the ProteinShop software designed to thoroughly sample a protein conformational space given the protein's sequence of amino acids and secondary structure predictions. It targets proteins with beta sheets because they are particularly challenging to predict due to the complexity of sampling long-range strand pairings. Here we discuss some of the most difficult targets in the recent 9th Community Wide Experiment on the Critical Assessment of Techniques for Protein Structure Prediction (CASP9) and show how BuildBeta can leverage some of the most successful methods in the category "template-free modeling" by augmenting their sampling capabilities. We also discuss ongoing efforts to improve the quality of the supersecondary structures it generates. PMID:22987350

  11. Cereal beta-glucans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cereal beta-glucans occur predominantly in oats and barley, but can be found in other cereals. Beta-glucan structure is a mixture of single beta-1,3-linkages and consecutive beta-1,4-linkages, and cellotriosyl and cellotetraosyl units typically make up 90-95% of entire molecule. Lichenase can hydr...

  12. Synthetic peptide homologous to. beta. protein from Alzheimer's disease forms amyloid-like fibrils in vitro

    SciTech Connect

    Kirschner, D.A.; Inouye, H.; Duffy, L.K.; Sinclair, A.; Lind, M.; Selkoe, D.J.

    1987-10-01

    Progressive amyloid deposition in senile plaques and cortical blood vessels may play a central role in the pathogenesis of Alzheimer's disease. The authors have used x-ray diffraction and electron microscopy to study the molecular organization and morphology of macromolecular assemblies formed by three synthetic peptides homologous to ..beta.. protein of brain amyloid: ..beta..-(1-28), residues 1-28 of the ..beta.. protein; (Ala/sup 1 -/..beta..-(1-28), ..beta..-(1-28) with alanine substituted for lysine at position 16; and ..beta..-(18-28), residues 18-28 of the ..beta.. protein. ..beta..-(1-28) readily formed fibrils in vitro that were similar in ultrastructure to the in vivo amyloid and aggregated into large bundles resembling those of senile plaque cores. X-ray patterns from partially dried, oriented pellets showed a cross-..beta..-conformation. (Ala/sup 16/)..beta..-(1-28) formed ..beta..-pleated sheet assemblies that were dissimilar to in vivo fibrils. The width of the 10-A spacing indicated stacks of about six sheets. Thus, substitution of the uncharged alanine for the positively charged lysine in the ..beta..-strand region enhances the packing of the sheets and dramatically alters the type of macromolecular aggregate formed. BETA-(18-28) formed assemblies that had even a greater number of stacked sheets. The findings on these homologous synthetic assemblies help to define the specific sequence that is required to form Alzheimer's-type amyloid fibrils, thus providing an in vitro model of age-related cerebral amyloidogenesis.

  13. A comparison of two different methods for formation of the beta phase in nanocomposites based on vinylidene fluoride-hexafluoropropylene copolymer

    NASA Astrophysics Data System (ADS)

    Borisova, Lyudmila; Kiryakova, Dimitrina; Atanassov, Atanas

    2014-06-01

    Nanocomposite materials based on vinylidene fluoride-hexafluoropropylene copolymer and organically modified montmorillonite Cloisite®15A were prepared by two different methods: melt mixing and co-precipitation. The changes taking place in crystalline structure, tensile strength, thermal behavior and the formation of piezoelectric b-phase as a result of the polymer system dissolution in dimethyl sulfoxide were studied. The technological specificity of each method has certain effect on the properties of the obtained nanocomposites. The highest content of b-phase — 95 % was achieved by co-precipitation from the solution of vinylidene fluoride-hexafluoropropylene copolymer in dimethyl sulfoxide and 6 mass % content of Cloisite®15A. Despite the common view that the use of solvents and prolonged technological procedure lead to overall higher expenses, the obtained nanocomposites could be promising for the preparation of new piezo-materials.

  14. Divergent effects of 17-{beta}-estradiol on human vascular smooth muscle and endothelial cell function diminishes TNF-{alpha}-induced neointima formation

    SciTech Connect

    Nintasen, Rungrat; Riches, Kirsten; Mughal, Romana S.; Viriyavejakul, Parnpen; Chaisri, Urai; Maneerat, Yaowapa; Turner, Neil A.; Porter, Karen E.

    2012-04-20

    Highlights: Black-Right-Pointing-Pointer TNF-{alpha} augments neointimal hyperplasia in human saphenous vein. Black-Right-Pointing-Pointer TNF-{alpha} induces detrimental effects on endothelial and smooth muscle cell function. Black-Right-Pointing-Pointer Estradiol exerts modulatory effects on TNF-induced vascular cell functions. Black-Right-Pointing-Pointer The modulatory effects of estradiol are discriminatory and cell-type specific. -- Abstract: Coronary heart disease (CHD) is a condition characterized by increased levels of proinflammatory cytokines, including tumor necrosis factor-{alpha} (TNF-{alpha}). TNF-{alpha} can induce vascular endothelial cell (EC) and smooth muscle cell (SMC) dysfunction, central events in development of neointimal lesions. The reduced incidence of CHD in young women is believed to be due to the protective effects of estradiol (E2). We therefore investigated the effects of TNF-{alpha} on human neointima formation and SMC/EC functions and any modulatory effects of E2. Saphenous vein (SV) segments were cultured in the presence of TNF-{alpha} (10 ng/ml), E2 (2.5 nM) or both in combination. Neointimal thickening was augmented by incubation with TNF-{alpha}, an effect that was abolished by co-culture with E2. TNF-{alpha} increased SV-SMC proliferation in a concentration-dependent manner that was optimal at 10 ng/ml (1.5-fold increase), and abolished by E2 at all concentrations studied (1-50 nM). Surprisingly, E2 itself at low concentrations (1 and 5 nM) stimulated SV-SMC proliferation to a level comparable to that of TNF-{alpha} alone. SV-EC migration was significantly impaired by TNF-{alpha} (42% of control), and co-culture with E2 partially restored the ability of SV-EC to migrate and repair the wound. In contrast, TNF-{alpha} increased SV-SMC migration by 1.7-fold, an effect that was completely reversed by co-incubation with E2. Finally, TNF-{alpha} potently induced ICAM-1 and VCAM-1 expression in both SV-EC and SV-SMC. However there

  15. Mechanism of inactivation of alanine racemase by beta, beta, beta-trifluoroalanine

    SciTech Connect

    Faraci, W.S.; Walsh, C.T.

    1989-01-24

    The alanine racemases are a group of PLP-dependent bacterial enzymes that catalyze the racemization of alanine, providing D-alanine for cell wall synthesis. Inactivation of the alanine racemases from the Gram-negative organism Salmonella typhimurium and Gram-positive organism Bacillus stearothermophilus with beta, beta, beta-trifluoroalanine has been studied. The inactivation occurs with the same rate constant as that for formation of a broad 460-490-nm chromophore. Loss of two fluoride ions per mole of inactivated enzyme and retention of (1-/sup 14/C)trifluoroalanine label accompany inhibition, suggesting a monofluoro enzyme adduct. Partial denaturation (1 M guanidine) leads to rapid return of the initial 420-nm chromophore, followed by a slower (t1/2 approximately 30 min-1 h) loss of the fluoride ion and /sup 14/CO/sub 2/ release. At this point, reduction by NaB/sub 3/H/sub 4/ and tryptic digestion yield a single radiolabeled peptide. Purification and sequencing of the peptide reveals that lysine-38 is covalently attached to the PLP cofactor. A mechanism for enzyme inactivation by trifluoroalanine is proposed and contrasted with earlier results on monohaloalanines, in which nucleophilic attack of released aminoacrylate on the PLP aldimine leads to enzyme inactivation. For trifluoroalanine inactivation, nucleophilic attack of lysine-38 on the electrophilic beta-difluoro-alpha, beta-unsaturated imine provides an alternative mode of inhibition for these enzymes.

  16. Interhemispheric Ice-Sheet Synchronicity During the Last Glacial Maximum

    NASA Astrophysics Data System (ADS)

    Weber, M. E.; Clark, P. U.; Kuhn, G.; Ricken, W.; Sprenk, D.

    2011-12-01

    The timing of the last maximum extent of the Antarctic ice sheets relative to those in the Northern Hemisphere remains poorly understood because only a few findings with robust chronologies exist for Antarctic ice sheets. We developed a chronology for the Weddell Sea sector of the East Antarctic ice sheet that, combined with ages from other Antarctic ice-sheet sectors, indicates the advance to and retreat from their maximum extent was nearly synchronous with Northern Hemisphere ice sheets. As for the deglaciation, modeling studies suggest a late ice-sheet retreat starting around 14 ka BP and ending around 7 ka BP with a large impact of an unstable West Antarctic Ice Sheet (WAIS) and a small impact of a stable East Antarctic Ice Sheet (EAIS). However, the Weddell Sea sites studied here, as well as sites from the Scotia Sea, provide evidence that specifically the EAIS responded much earlier, possibly provided a significant contribution to the last sea-level rise, and was much more dynamic than previously thought. Deep-sea sediment sites from the central Scotia Sea "iceberg alley" show four phases of enhanced deposition of ice-rated detritus (IRD) occurred at 19.5, 16.5,14.5, and 12 ka. The first two relate to the two ice-sheet retreat signals documented for the Weddell Sea; the third phase indicates an Antarctic component to meltwater pulse 1a; the fourth phase falls roughly into period of the Younger Dryas. Our modeling studies show that surface climate forcing of Antarctic ice sheets would have likely increased ice mass balance during deglaciation, whereby a warming climate would increase accumulation but not surface melting. We propose that sea-level forcing from Northern Hemisphere ice sheets and changes in North Atlantic deepwater formation and attendant heat flux to Antarctic grounding lines provided the teleconnections to synchronize the hemispheric ice sheets.

  17. Effects of mutations in the {beta} subunit hinge domain on ATP synthase F{sub 1} sector rotation: Interaction between Ser 174 and Ile 163

    SciTech Connect

    Kashiwagi, Sachiko; Iwamoto-Kihara, Atsuko; Kojima, Masaki; Nonaka, Takamasa; Futai, Masamitsu Nakanishi-Matsui, Mayumi

    2008-01-11

    A complex of {gamma}, {epsilon}, and c subunits rotates in ATP synthase (F{sub o}F{sub 1}) coupling with proton transport. Replacement of {beta}Ser174 by Phe in {beta}-sheet4 of the {beta} subunit ({beta}S174F) caused slow {gamma} subunit revolution of the F{sub 1} sector, consistent with the decreased ATPase activity [M. Nakanishi-Matsui, S. Kashiwagi, T. Ubukata, A. Iwamoto-Kihara, Y. Wada, M. Futai, Rotational catalysis of Escherichia coli ATP synthase F1 sector. Stochastic fluctuation and a key domain of the {beta} subunit, J. Biol. Chem. 282 (2007) 20698-20704]. Modeling of the domain including {beta}-sheet4 and {alpha}-helixB predicted that the mutant {beta}Phe174 residue undergoes strong and weak hydrophobic interactions with {beta}Ile163 and {beta}Ile166, respectively. Supporting this prediction, the replacement of {beta}Ile163 in {alpha}-helixB by Ala partially suppressed the {beta}S174F mutation: in the double mutant, the revolution speed and ATPase activity recovered to about half of the levels in the wild-type. Replacement of {beta}Ile166 by Ala lowered the revolution speed and ATPase activity to the same levels as in {beta}S174F. Consistent with the weak hydrophobic interaction, {beta}Ile166 to Ala mutation did not suppress {beta}S174F. Importance of the hinge domain [phosphate-binding loop (P-loop)/{alpha}-helixB/loop/{beta}-sheet4, {beta}Phe148-{beta}Gly186] as to driving rotational catalysis is discussed.

  18. Absorption of Beta Particles in Different Materials: An Undergraduate Experiment

    ERIC Educational Resources Information Center

    La Rocca, Paola; Riggi, Francesco

    2009-01-01

    The absorption of beta rays from a radioactive source in different materials was investigated by the use of a simple setup based on a Geiger counter and a set of absorber sheets. The number of electrons traversing the material was measured as a function of its thickness. Detailed GEANT simulations were carried out to reproduce the obtained…

  19. New hydrolysis products of the beta-lactam antibiotic amoxicillin, their pH-dependent formation and search in municipal wastewater.

    PubMed

    Hirte, Kristin; Seiwert, Bettina; Schüürmann, Gerrit; Reemtsma, Thorsten

    2016-01-01

    Amoxicillin (AMX) is a widespread β-lactam-antibiotic and, together with some of its transformation products (TPs) originating from hydrolysis, a known environmental contaminant. To shed light on the abiotic degradation of AMX and the stability of its known TPs, laboratory hydrolysis experiments of AMX were carried out at pH 3, 7 and 11. Not only the rate of hydrolysis but also the pattern of TPs was strongly pH-dependent. The time courses of the obtained transformation products were analyzed by UPLC-HR-QToF-MS. AMX penicilloic acid (TP 1), AMX 2',5'-diketopiperazine (TP 2), AMX penilloic acid (TP 3) and 3-(4-hydroxyphenyl)pyrazinol (TP 4) were found at neutral pH. Surprisingly, the first three were not stable but transformed into 23 yet unknown TPs within three to four weeks. Seven TPs were tentatively identified, based on their product ion spectra and, where possible, confirmed with reference standards, e.g. penicillamine disulfide, 2-[amino(carboxy)methyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid and dehydrocarboxylated amoxicillin penilloic acid. Analysis of samples from municipal wastewater treatment plants confirmed these findings with TP 1 being the dominant TP in the influent and a shift towards TP 2, TP 3 and TP 4 in the effluents. The lab experiments predicted up to 13 consecutive TPs from TP 1, TP 2 and TP 3 under neutral conditions. Their detection from surface waters will be difficult, because their large number and slow formation kinetics will lead to comparatively low environmental concentrations. Nevertheless the abiotic degradation of TP 1, TP 2 and TP 3 to further TPs needs to be considered in future studies of the environmental fate of amoxicillin.

  20. A synopsis of factors regulating beta cell development and beta cell mass.

    PubMed

    Prasadan, Krishna; Shiota, Chiyo; Xiangwei, Xiao; Ricks, David; Fusco, Joseph; Gittes, George

    2016-10-01

    The insulin-secreting beta cells in the endocrine pancreas regulate blood glucose levels, and loss of functional beta cells leads to insulin deficiency, hyperglycemia (high blood glucose) and diabetes mellitus. Current treatment strategies for type-1 (autoimmune) diabetes are islet transplantation, which has significant risks and limitations, or normalization of blood glucose with insulin injections, which is clearly not ideal. The type-1 patients can lack insulin counter-regulatory mechanism; therefore, hypoglycemia is a potential risk. Hence, a cell-based therapy offers a better alternative for the treatment of diabetes. Past research was focused on attempting to generate replacement beta cells from stem cells; however, recently there has been an increasing interest in identifying mechanisms that will lead to the conversion of pre-existing differentiated endocrine cells into beta cells. The goal of this review is to provide an overview of several of the key factors that regulate new beta cell formation (neogenesis) and beta cell proliferation. PMID:27105622

  1. Temperature Dependence of Positron Annihilation in beta-Cyclodextrin and beta-Cyclodextrin Complexes

    NASA Astrophysics Data System (ADS)

    Hu, Y.; Hsu Hadley, F. H., Jr.; Trinh, T.

    1996-11-01

    The effects of temperature on positron annihilation in beta-cyclodextrin and beta-cyclodextrin complexed with benzyl salicylate, benzyl acetate, ethyl salicylate, geraniol, linalool and nerol were studied. Samples were prepared by slurry, air-dried and freeze-dried methods. Lifetime spectra were measured as a function of temperature for each sample. Comparison of the annihilation rate and intensity of the longer-lived component showed that positronium formation was affected by guest molecules, preparation methods and temperature variations. Results can be used to explain beta-cyclodextrin complex formation with different guest molecules.

  2. Beta titanium alloys in the 80's; Proceedings of the Symposium, Atlanta, GA, March 8, 1983

    SciTech Connect

    Boyer, R.R.; Rosenberg, H.W.

    1984-01-01

    Among the topics discussed are the use of beta-Ti in the SR-71 aircraft, the microstructure and properties of beta-Ti alloys, the effects of hydrogen, heat treatment, and omega-phase formation on beta-Ti, the primary processing of beta- and near-beta-Ti alloys, the processing window for grain size control in metastable beta-Ti, grain growth in beta III-Ti, the processing and properties of Ti-17 alloy for aircraft and turbine applications, the isothermal forging of beta- and near-beta-Ti alloys, the torsional properties of beta-Ti in automotive suspension springs, and the martensitic Transage Ti alloys. Also covered are Ti-Nb superconductors, and property compilations for such commercial and developmental beta-Ti alloys as beta-III, Ti-15-3, Ti-17, Transage 134, and cast and wrought Transage 175.

  3. Energy information sheets

    SciTech Connect

    Not Available

    1993-12-02

    The National Energy Information Center (NEIC), as part of its mission, provides energy information and referral assistance to Federal, State, and local governments, the academic community, business and industrial organizations, and the general public. Written for the general public, the EIA publication Energy Information Sheets was developed to provide information on various aspects of fuel production, prices, consumption and capability. The information contained herein pertains to energy data as of December 1991. Additional information on related subject matter can be found in other EIA publications as referenced at the end of each sheet.

  4. Light sheet microscopy.

    PubMed

    Weber, Michael; Mickoleit, Michaela; Huisken, Jan

    2014-01-01

    This chapter introduces the concept of light sheet microscopy along with practical advice on how to design and build such an instrument. Selective plane illumination microscopy is presented as an alternative to confocal microscopy due to several superior features such as high-speed full-frame acquisition, minimal phototoxicity, and multiview sample rotation. Based on our experience over the last 10 years, we summarize the key concepts in light sheet microscopy, typical implementations, and successful applications. In particular, sample mounting for long time-lapse imaging and the resulting challenges in data processing are discussed in detail.

  5. A Logical OR Redundancy within the Asx-Pro-Asx-Gly Type 1 {Beta}-Turn Motif

    SciTech Connect

    Lee, Jihun; Dubey, Vikash Kumar; Longo, Lian M.; Blaber, Michael

    2008-04-19

    Turn secondary structure is essential to the formation of globular protein architecture. Turn structures are, however, much more complex than either {alpha}-helix or {beta}-sheet, and the thermodynamics and folding kinetics are poorly understood. Type I {beta}-turns are the most common type of reverse turn, and they exhibit a statistical consensus sequence of Asx-Pro-Asx-Gly (where Asx is Asp or Asn). A comprehensive series of individual and combined Asx mutations has been constructed within three separate type I 3:5 G1 bulge {beta}-turns in human fibroblast growth factor-1, and their effects on structure, stability, and folding have been determined. The results show a fundamental logical OR relationship between the Asx residues in the motif, involving H-bond interactions with main-chain amides within the turn. These interactions can be modulated by additional interactions with residues adjacent to the turn at positions i + 4 and i + 6. The results show that the Asx residues in the turn motif make a substantial contribution to the overall stability of the protein, and the Asx logical OR relationship defines a redundant system that can compensate for deleterious point mutations. The results also show that the stability of the turn is unlikely to be the prime determinant of formation of turn structure in the folding transition state.

  6. Physicochemical properties and interactions of Escherichia coli ribonucleic acid polymerase holoenzyme, core enzyme, subunits, and subassembly alpha 2 beta.

    PubMed

    Levine, B J; Orphanos, P D; Fischmann, B S; Beychok, S

    1980-10-14

    We have investigated several physicochemical properties of Escherichia coli DNA-dependent RNa polymerase, its constituent subunits alpha, beta, beta', and sigma, and the subassembly alpha 2 beta. These included ultraviolet (UV) absorption, isoelectric points, sulfhydryl content, extinction coefficients, and circular dichroism (CD). Among the most notable results is the observation, based on CD measurements, that the sigma subunit, free and combined in holoenzyme, is a highly structured protein with approximately 75% of its residues folded in alpha-helical conformation and little or no detectable beta sheet. No secondary structure changes in either sigma or core accompany formation of holoenzyme. In contrast to the conformational independence of the subunits in assembly of holoenzyme, the protein and its components exhibit conformational flexibility as glycerol concentration is varied and in their interaction with DNA. The effect of glycerol on the conformation of sigma, core, and holoenzyme was monitored by circular dichroism measurements. In the far-ultraviolet, the residue ellipticity at 220 nm ([theta]220) increased approximately 15% from 0 to 10% glycerol for both core and holoenzyme. In the near-ultraviolet, the residue ellipticity at a peak near 280 nm also varied with glycerol concentration, decreasing in intensity by about 50% with holoenzyme, when glycerol was raised from 5 to 10%, then increasing at still higher glycerol contents. Electrophoretic and molecular sieve anaysis showed core and sigma to have greater affinity for each other in 50% glycerol than in 10% glycerol. The presence of 10% glycerol in the assay buffer increased the activity of the enzyme. The effect of various DNA templates on the conformations of core, holoenzyme, alpha 2 beta subassembly, and beta' subunit was also monitored by far-ultraviolet circular dichroism. All the protein samples showed between 10 and 20% decrease in secondary structure upon the addition of the DNA. PMID

  7. Ferulic acid destabilizes preformed {beta}-amyloid fibrils in vitro

    SciTech Connect

    Ono, Kenjiro; Hirohata, Mie; Yamada, Masahito . E-mail: m-yamada@med.kanazawa-u.ac.jp

    2005-10-21

    Inhibition of the formation of {beta}-amyloid fibrils (fA{beta}), as well as the destabilization of preformed fA{beta} in the CNS, would be attractive therapeutic targets for the treatment of Alzheimer's disease (AD). We reported previously that curcumin (Cur) inhibits fA{beta} formation from A{beta} and destabilizes preformed fA{beta} in vitro. Using fluorescence spectroscopic analysis with thioflavin T and electron microscopic studies, we examined the effects of ferulic acid (FA) on the formation, extension, and destabilization of fA{beta} at pH 7.5 at 37 deg C in vitro. We next compared the anti-amyloidogenic activities of FA with Cur, rifampicin, and tetracycline. Ferulic acid dose-dependently inhibited fA{beta} formation from amyloid {beta}-peptide, as well as their extension. Moreover, it destabilized preformed fA{beta}s. The overall activity of the molecules examined was in the order of: Cur > FA > rifampicin = tetracycline. FA could be a key molecule for the development of therapeutics for AD.

  8. 5. Historic American Buildings Survey Taken from drawing sheet, SHEET ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. Historic American Buildings Survey Taken from drawing sheet, SHEET #21, Showing the house as restored since Survey. (Dormer windows omitted as not authentic) - Samuel des Marest House, River Road, New Milford, Bergen County, NJ

  9. 71. PALMDALE WATER COMPANY, EASTWOOD MULTIPLEARCHED DAM: STRESS SHEET, SHEET ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    71. PALMDALE WATER COMPANY, EASTWOOD MULTIPLE-ARCHED DAM: STRESS SHEET, SHEET 3; DECEMBER 20, 1918. Littlerock Water District files. - Little Rock Creek Dam, Little Rock Creek, Littlerock, Los Angeles County, CA

  10. Effects of electron pressure anisotropy on current sheet configuration

    NASA Astrophysics Data System (ADS)

    Artemyev, A. V.; Vasko, I. Y.; Angelopoulos, V.; Runov, A.

    2016-09-01

    Recent spacecraft observations in the Earth's magnetosphere have demonstrated that the magnetotail current sheet can be supported by currents of anisotropic electron population. Strong electron currents are responsible for the formation of very thin (intense) current sheets playing the crucial role in stability of the Earth's magnetotail. We explore the properties of such thin current sheets with hot isotropic ions and cold anisotropic electrons. Decoupling of the motions of ions and electrons results in the generation of a polarization electric field. The distribution of the corresponding scalar potential is derived from the electron pressure balance and the quasi-neutrality condition. We find that electron pressure anisotropy is partially balanced by a field-aligned component of this polarization electric field. We propose a 2D model that describes a thin current sheet supported by currents of anisotropic electrons embedded in an ion-dominated current sheet. Current density profiles in our model agree well with THEMIS observations in the Earth's magnetotail.

  11. Low-Temperature Forming of Beta Titanium Alloys

    NASA Technical Reports Server (NTRS)

    Kaneko, R. S.; Woods, C. A.

    1983-01-01

    Low cost methods for titanium structural fabrication using advanced cold-formable beta alloys were investigated for application in a Mach 2.7 supersonic cruise vehicle. This work focuses on improving processing and structural efficiencies as compared with standard hot formed and riveted construction of alpha-beta alloy sheet structure. Mechanical property data and manufacturing parameters were developed for cold forming, brazing, welding, and processing Ti-15V-3Cr-3Sn-3Al sheet, and Ti-3Al-8V-6Cr-4Zr on a more limited basis. Cost and structural benefits were assessed through the fabrication and evaluation of large structural panels. The feasibility of increasing structural efficiency of beta titanium structure by selective reinforcement with metal matrix composite was also explored.

  12. Effect of initial stagger selection on the handedness of Amyloid beta helical fibrils

    SciTech Connect

    Ghattyvenkatakrishna, Pavan K; Cheng, Xiaolin; Uberbacher, Edward C

    2013-01-01

    Various structural models for Amyloid $\\beta$ fibrils derived from a variety of experimental techniques are currently available. However, this data cannot differentiate between the relative position of the two arms of the $\\beta$ hairpin called the stagger. Amyloid fibrils of various heirarchical levels form left--handed helices composed of $\\beta$ sheets. However it is unclear if positive, negative and neutral staggers all form the macroscopic left--handed helices. Studying this is important since the success of computational approaches to develop drugs for amyloidic diseases will depend on selecting the physiologically relevant structure of the sheets. To address this issue we have conducted extensive molecular dynamics simulations of Amyloid$\\beta$ sheets of various staggers and show that only negative staggers generate the experimentally observed left--handed helices while positive staggers generate the incorrect right--handed helices. The implications of this result extend in to all amyloidic--aggregation type diseases.

  13. beta-Hexachlorocyclohexane (beta-HCH)

    Integrated Risk Information System (IRIS)

    beta - Hexachlorocyclohexane ( beta - HCH ) ; CASRN 319 - 85 - 7 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Asses

  14. Modeling the formation of secondary organic aerosol (SOA). 2. The predicted effects of relative humidity on aerosol formation in the alpha-pinene-, beta-pinene-, sabinene-, delta 3-carene-, and cyclohexene-ozone systems.

    PubMed

    Seinfeld, J H; Erdakos, G B; Asher, W E; Pankow, J F

    2001-05-01

    Atmospheric oxidation of volatile organic compounds can lead to the formation of secondary organic aerosol (SOA) through the gas/particle (G/P) partitioning of the oxidation products. Since water is ubiquitous in the atmosphere, the extent of the partitioning for any individual organic product depends not only on the amounts and properties of the partitioning organic compounds, but also on the amount of water present. Predicting the effects of water on the atmospheric G/P distributions of organic compounds is, therefore, central to understanding SOA formation. The goals of the current work are to gain understanding of how increases in RH affect (1) overall SOA yields, (2) water uptake by SOA, (3) the behaviors of individual oxidation products, and (4) the fundamental physical properties of the SOA phase that govern the G/P distribution of each of the oxidation products. Part 1 of this series considered SOA formation from five parent hydrocarbons in the absence of water. This paper predicts how adding RH to those systems uniformly increases both the amount of condensed organic mass and the amount of liquid water in the SOA phase. The presence of inorganic components is not considered. The effect of increasing RH is predicted to be stronger for SOA produced from cyclohexene as compared to SOA produced from four monoterpenes. This is likely a result of the greater general degree of oxidation (and hydrophilicity) of the cyclohexene products. Good agreement was obtained between predicted SOA yields and laboratory SOA yield data actually obtained in the presence of water. As RH increases, the compounds that play the largest roles in changing both the organic and water masses in the SOA phase are those with vapor pressures that are intermediate between those of essentially nonvolatile and highly volatile species. RH-driven changes in the compound-dependent G/P partitioning coefficient Kp result from changes in both the average molecular weight MWom of the absorbing

  15. Quick Information Sheets. 1988.

    ERIC Educational Resources Information Center

    Wisconsin Univ., Madison. Trace Center.

    The Trace Center gathers and organizes information on communication, control, and computer access for handicapped individuals. The information is disseminated in the form of brief sheets describing print, nonprint, and organizational resources and listing addresses and telephone numbers for ordering or for additional information. This compilation…

  16. Quick Information Sheets.

    ERIC Educational Resources Information Center

    Wisconsin Univ., Madison. Trace Center.

    This compilation of "Trace Quick Sheets" provides descriptions, prices, and ordering information for products and services that assist with communication, control, and computer access for disabled individuals. Product descriptions or product sources are included for: adaptive toys and toy modifications; head pointers, light pointers, and…

  17. Ethanol Myths Fact Sheet

    SciTech Connect

    2009-10-27

    Ethanol is a clean, renewable fuel that is helping to reduce our nation’s dependence on oil and can offer additional economic and environmental benefits in the future. This fact sheet is intended to address some common misconceptions about this important alternative fuel.

  18. Insulation Fact Sheet.

    ERIC Educational Resources Information Center

    Conservation and Renewable Energy Inquiry and Referral Service (DOE), Silver Spring, MD.

    Heating and cooling account for 50-70% of the energy consumed in the average American home. Heating water accounts for another 20%. A poorly insulated home loses much of this energy, causing drafty rooms and high energy bills. This fact sheet discusses how to determine if your home needs more insulation, the additional thermal resistance (called…

  19. Ethanol Basics (Fact Sheet)

    SciTech Connect

    Not Available

    2015-01-01

    Ethanol is a widely-used, domestically-produced renewable fuel made from corn and other plant materials. More than 96% of gasoline sold in the United States contains ethanol. Learn more about this alternative fuel in the Ethanol Basics Fact Sheet, produced by the U.S. Department of Energy's Clean Cities program.

  20. Reading Recovery. [Fact Sheets].

    ERIC Educational Resources Information Center

    Reading Recovery Council of North America, Columbus, OH.

    This set of 10 fact sheets (each 2 to 4 pages long) addresses aspects of Reading Recovery, a program that helps children to be proficient readers and writers by the end of the first grade. It discusses the basic facts of Reading Recovery; Reading Recovery for Spanish literacy; Reading Recovery lessons; Reading Recovery professional development;…

  1. Algal Biofuels Fact Sheet

    SciTech Connect

    2009-10-27

    This fact sheet provides information on algal biofuels, which are generating considerable interest around the world. They may represent a sustainable pathway for helping to meet the U.S. biofuel production targets set by the Energy Independence and Security Act of 2007.

  2. Interhemispheric ice-sheet synchronicity during the Last Glacial Maximum

    NASA Astrophysics Data System (ADS)

    Weber, M. E.; Clark, P. U.; Ricken, W.; Mitrovica, J. X.; Hostetler, S. W.; Kuhn, G.

    2012-04-01

    The timing of the last maximum extent of the Antarctic ice sheets relative to those in the Northern Hemisphere remains poorly understood because only a few findings with robust chronologies exist for Antarctic ice sheets. We developed a chronology for the Weddell Sea sector of the East Antarctic ice sheet that, combined with ages from other Antarctic ice-sheet sectors, indicates the advance to their maximum extent at 29 -28 ka, and retreat from their maximum extent at 19 ka was nearly synchronous with Northern Hemisphere ice sheets (Weber, M.E., Clark, P. U., Ricken, W., Mitrovica, J. X., Hostetler, S. W., and Kuhn, G. (2011): Interhemispheric ice-sheet synchronicity during the Last Glacial Maximum. - Science, 334, 1265-1269, doi: 10.1126:science.1209299). As for the deglaciation, modeling studies suggest a late ice-sheet retreat starting around 14 ka BP and ending around 7 ka BP with a large impact of an unstable West Antarctic Ice Sheet (WAIS) and a small impact of a stable East Antarctic Ice Sheet (EAIS). However, the Weddell Sea sites studied here, as well as sites from the Scotia Sea, provide evidence that specifically the EAIS responded much earlier, possibly provided a significant contribution to the last sea-level rise, and was much more dynamic than previously thought. Using the results of an atmospheric general circulation we conclude that surface climate forcing of Antarctic ice mass balance would likely cause an opposite response, whereby a warming climate would increase accumulation but not surface melting. Furthermore, our new data support teleconnections involving a sea-level fingerprint forced from Northern Hemisphere ice sheets as indicated by gravitational modeling. Also, changes in North Atlantic Deepwater formation and attendant heat flux to Antarctic grounding lines may have contributed to synchronizing the hemispheric ice sheets.

  3. Core binding factor beta (Cbfβ) controls the balance of chondrocyte proliferation and differentiation by upregulating Indian hedgehog (Ihh) expression and inhibiting parathyroid hormone-related protein receptor (PPR) expression in postnatal cartilage and bone formation.

    PubMed

    Tian, Fei; Wu, Mengrui; Deng, Lianfu; Zhu, Guochun; Ma, Junqing; Gao, Bo; Wang, Lin; Li, Yi-Ping; Chen, Wei

    2014-07-01

    Core binding factor beta (Cbfβ) is essential for embryonic bone morphogenesis. Yet the mechanisms by which Cbfβ regulates chondrocyte proliferation and differentiation as well as postnatal cartilage and bone formation remain unclear. Hence, using paired-related homeobox transcription factor 1-Cre (Prx1-Cre) mice, mesenchymal stem cell-specific Cbfβ-deficient (Cbfβ(f/f) Prx1-Cre) mice were generated to study the role of Cbfβ in postnatal cartilage and bone development. These mutant mice survived to adulthood but exhibited severe sternum and limb malformations. Sternum ossification was largely delayed in the Cbfβ(f/f) Prx1-Cre mice and the xiphoid process was noncalcified and enlarged. In newborn and 7-day-old Cbfβ(f/f) Prx1-Cre mice, the resting zone was dramatically elongated, the proliferation zone and hypertrophic zone of the growth plates were drastically shortened and disorganized, and trabecular bone formation was reduced. Moreover, in 1-month-old Cbfβ(f/f) Prx1-Cre mice, the growth plates were severely deformed and trabecular bone was almost absent. In addition, Cbfβ deficiency impaired intramembranous bone formation both in vivo and in vitro. Interestingly, although the expression of Indian hedgehog (Ihh) was largely reduced, the expression of parathyroid hormone-related protein (PTHrP) receptor (PPR) was dramatically increased in the Cbfβ(f/f) Prx1-Cre growth plate, indicating that that Cbfβ deficiency disrupted the Ihh-PTHrP negative regulatory loop. Chromatin immunoprecipitation (ChIP) analysis and promoter luciferase assay demonstrated that the Runx/Cbfβ complex binds putative Runx-binding sites of the Ihh promoter regions, and also the Runx/Cbfβ complex directly upregulates Ihh expression at the transcriptional level. Consistently, the expressions of Ihh target genes, including CyclinD1, Ptc, and Pthlh, were downregulated in Cbfβ-deficient chondrocytes. Taken together, our study reveals not only that Cbfβ is essential for chondrocyte

  4. Characteristics of liquid sheets formed by splash plate nozzles

    NASA Astrophysics Data System (ADS)

    Ahmed, M.; Amighi, A.; Ashgriz, N.; Tran, H. N.

    2008-01-01

    An experimental study was conducted to identify the effect of viscosity on the characteristics of liquid sheets formed by a splash plate nozzle. Various mixtures of corn syrup and water are used to obtain viscosities in the range 1-170 mPa.s. Four different splash plates with nozzle diameters of 0.5, 0.75, 1, and 2 mm, with a constant plate angle of 55° were tested. Liquid sheets formed under various operating conditions were directly visualized. The sheet atomization process for the range of parameters studied here is governed by two different mechanisms: Rayleigh-Plateau (R-P) and Rayleigh-Taylor (R-T) instabilities. R-P occurs at the rim and R-T occurs on the thin sheet. The rim instability can be laminar or turbulent, depending on the jet Reynolds number. The R-T instability of the sheet is observed at the outer edges of the radially spreading sheet, where the sheet is the thinnest. It can also occur inside the sheet, due to formation of holes and ruptures.

  5. Origami folding of polymer sheets by inkjet printing

    NASA Astrophysics Data System (ADS)

    Liu, Ying; Shaw, Brandi; Dickey, Michael D.; Genzer, Jan

    2015-03-01

    In analogy to the ancient Japanese art of paper folding (Origami), self-folding is an attractive strategy to induce the formation of three-dimensional (3D) objects with well-defined shapes and dimensions using conventional two-dimensional (2D) patterning techniques, such as lithography and inkjet printing. Self-folding can be applied in the areas of reconfigurable devices, actuators, and sensors. Here we demonstrate a simple method for self-folding of polymer sheets utilizing localized light absorption on selected areas of the pre-strained polymer sheet. The ink is patterned via a desktop printer and it defines the location of the `hinge' on the sheet. The inked areas on the 2D sheet absorb light preferentially, thus causing the polymer sheet to fold locally in the inked areas. The temperature gradients through the depth of the sheet induce localized shrinkage and the sheet folds within seconds. This patterned polymer sheets act as shape memory materials which can be programmed to fold into various 3D structures based on the nature of the light source, the shape and size of the ink patterns, and ink property. By controlling the aforementioned parameters we achieve a complete control of the time and degree of folding, which ultimately govern the final 3D shape of the folded object.

  6. Raman and AFM study of gamma irradiated plastic bottle sheets

    NASA Astrophysics Data System (ADS)

    Ali, Yasir; Kumar, Vijay; Sonkawade, R. G.; Dhaliwal, A. S.

    2013-02-01

    In this investigation, the effects of gamma irradiation on the structural properties of plastic bottle sheet are studied. The Plastic sheets were exposed with 1.25MeV 60Co gamma rays source at various dose levels within the range from 0-670 kGy. The induced modifications were followed by micro-Raman and atomic force microscopy (AFM). The Raman spectrum shows the decrease in Raman intensity and formation of unsaturated bonds with an increase in the gamma dose. AFM image displays rough surface morphology after irradiation. The detailed Raman analysis of plastic bottle sheets is presented here, and the results are correlated with the AFM observations.

  7. Raman and AFM study of gamma irradiated plastic bottle sheets

    SciTech Connect

    Ali, Yasir; Kumar, Vijay; Dhaliwal, A. S.; Sonkawade, R. G.

    2013-02-05

    In this investigation, the effects of gamma irradiation on the structural properties of plastic bottle sheet are studied. The Plastic sheets were exposed with 1.25MeV {sup 60}Co gamma rays source at various dose levels within the range from 0-670 kGy. The induced modifications were followed by micro-Raman and atomic force microscopy (AFM). The Raman spectrum shows the decrease in Raman intensity and formation of unsaturated bonds with an increase in the gamma dose. AFM image displays rough surface morphology after irradiation. The detailed Raman analysis of plastic bottle sheets is presented here, and the results are correlated with the AFM observations.

  8. Skill Sheets for Agricultural Mechanics.

    ERIC Educational Resources Information Center

    Iowa State Univ. of Science and Technology, Ames. Dept. of Agricultural Education.

    This set of 33 skill sheets for agricultural mechanics was developed for use in high school and vocational school agricultural mechanics programs. Some sheets teach operational procedures while others are for simple projects. Each skill sheet covers a single topic and includes: (1) a diagram, (2) a step-by-step construction or operational…

  9. The Physics of Ice Sheets

    ERIC Educational Resources Information Center

    Bassis, J. N.

    2008-01-01

    The great ice sheets in Antarctica and Greenland are vast deposits of frozen freshwater that contain enough to raise sea level by approximately 70 m if they were to completely melt. Because of the potentially catastrophic impact that ice sheets can have, it is important that we understand how ice sheets have responded to past climate changes and…

  10. Binding of cationic peptides (KX)4K to DPPG bilayers. Increasing the hydrophobicity of the uncharged amino acid X drives formation of membrane bound β-sheets: A DSC and FT-IR study.

    PubMed

    Hädicke, André; Blume, Alfred

    2016-06-01

    The binding of cationic peptides of the sequence (KX)4K to lipid vesicles of negatively charged dipalmitoyl-phosphatidylglycerol (DPPG) was investigated by differential scanning calorimetry (DSC) and temperature dependent Fourier-transformed infrared (FT-IR) spectroscopy. The hydrophobicity of the uncharged amino acid X was changed from G (glycine) over A (alanine), Abu (α-aminobutyric acid), V (valine) to L (leucine). The binding of the peptides caused an increase of the phase transition temperature (Tm) of DPPG by up to 20°C. The shift depended on the charge ratio and on the hydrophobicity of the amino acid X. Unexpectedly, the upward shift of Tm increased with increasing hydrophobicity of X. FT-IR spectroscopy showed a shift of the CH2 stretching vibrations of DPPG to lower frequency, particularly for bilayers in the liquid-crystalline phase, indicating an ordering of the hydrocarbon chains when the peptides were bound. Changes in the lipid C=O vibrational band indicated a dehydration of the lipid headgroup region after peptide binding. (KG)4K was bound in an unordered structure at all temperatures. All other peptides formed intermolecular antiparallel β-sheets, when bound to gel phase DPPG. However, for (KA)4K and (KAbu)4K, the β-sheets converted into an unordered structure above Tm. In contrast, the β-sheet structures of (KV)4K and (KL)4K remained stable even at 80°C when bound to the liquid-crystalline phase of DPPG. Strong aggregation of DPPG vesicles occurred after peptide binding. For the aggregates, we suggest a structure, where aggregated single β-sheets are sandwiched between opposing DPPG bilayers with a dehydrated interfacial region.

  11. Destabilization of 2D magnetic current sheets by resonance with bouncing electron - a new theory

    NASA Astrophysics Data System (ADS)

    Fruit, Gabriel; Louarn, Philippe; Tur, Anatoly

    2016-07-01

    In the general context of understanding the possible destabilization of the magnetotail before a substorm, we propose a kinetic model for electromagnetic instabilities in resonant interaction with trapped bouncing electrons. The geometry is clearly 2D and uses Harris sheet profile. Fruit et al. 2013 already used this model to investigate the possibilities of electrostatic instabilities. Tur et al. 2014 generalizes the model for full electromagnetic perturbations. Starting with a modified Harris sheet as equilibrium state, the linearized gyrokinetic Vlasov equation is solved for electromagnetic fluctuations with period of the order of the electron bounce period (a few seconds). The particle motion is restricted to its first Fourier component along the magnetic field and this allows the complete time integration of the non local perturbed distribution functions. The dispersion relation for electromagnetic modes is finally obtained through the quasi neutrality condition and the Ampere's law for the current density. The present talk will focus on the main results of this theory. The electrostatic version of the model may be applied to the near-Earth environment (8-12 R_{E}) where beta is rather low. It is showed that inclusion of bouncing electron motion may enhance strongly the growth rate of the classical drift wave instability. This model could thus explain the generation of strong parallel electric fields in the ionosphere and the formation of aurora beads with wavelength of a few hundreds of km. In the electromagnetic version, it is found that for mildly stretched current sheet (B_{z} > 0.1 B _{lobes}) undamped modes oscillate at typical electron bounce frequency with wavelength of the order of the plasma sheet thickness. As the stretching of the plasma sheet becomes more intense, the frequency of these normal modes decreases and beyond a certain threshold in B_{z}/B _{lobes}, the mode becomes explosive (pure imaginary frequency) with typical growing rate of a few

  12. Presentation of structured documents without a style sheet

    NASA Astrophysics Data System (ADS)

    Harrington, Steven J.; Wayman, Elizabeth

    2007-01-01

    In order to present most XML documents for human consumption, formatting information must be introduced and applied. Formatting is typically done through a style sheet, however, it is conceivable that one could wish to view the document without having a style sheet (either because a style sheet does not exist, or is unavailable, or is inappropriate for the display device). This paper describes a method for formatting structured documents without a provided style sheet. The idea is to first analyze the document to determine structures and features that might be relevant to style decisions. A transformation can be constructed to convert the original document to a generic form that captures the semantics that will be expressed through formatting and style. In the second stage styling is applied to the structures and features that have been discovered by applying a pre-defined style sheet for the generic form. The document instance, and if available, the corresponding schema or DTD can be analyzed in order to construct the transformation. This paper will describe the generic form used for formatting and techniques for generating transformations to it.

  13. Functional polymer sheet patterning using microfluidics.

    PubMed

    Li, Minggan; Humayun, Mouhita; Kozinski, Janusz A; Hwang, Dae Kun

    2014-07-22

    Poly(dimethylsiloxane) (PDMS)-based microfluidics provide a novel approach to advanced material synthesis. While PDMS has been successfully used in a wide range of industrial applications, due to the weak mechanical property channels generally possess low aspect ratios (AR) and thus produce microparticles with similarly low ARs. By increasing the channel width to nearly 1 cm, AR to 267, and implementing flow lithography, we were able to establish the slit-channel lithography. Not only does this allow us to synthesize sheet materials bearing multiscale features and tunable chemical anisotropy but it also allows us to fabricate functional layered sheet structures in a one-step, high-throughput fashion. We showcased the technique's potential role in various applications, such as the synthesis of planar material with micro- and nanoscale features, surface morphologies, construction of tubular and 3D layered hydrogel tissue scaffolds, and one-step formation of radio frequency identification (RFID) tags. The method introduced offers a novel route to functional sheet material synthesis and sheet system fabrication. PMID:24967616

  14. SHEET PLASMA DEVICE

    DOEpatents

    Henderson, O.A.

    1962-07-17

    An ion-electron plasma heating apparatus of the pinch tube class was developed wherein a plasma is formed by an intense arc discharge through a gas and is radially constricted by the magnetic field of the discharge. To avoid kink and interchange instabilities which can disrupt a conventional arc shortiy after it is formed, the apparatus is a pinch tube with a flat configuration for forming a sheet of plasma between two conductive plates disposed parallel and adjacent to the plasma sheet. Kink instabilities are suppressed by image currents induced in the conductive plates while the interchange instabilities are neutrally stable because of the flat plasma configuration wherein such instabilities may occur but do not dynamically increase in amplitude. (AEC)

  15. Plasma Sheet Energy Distributions

    NASA Astrophysics Data System (ADS)

    Sotirelis, T.; Lee, A. R.; Newell, P. T.

    2009-12-01

    Energy spectra of electrons and ions, as observed by DMSP, are fit to various distributions. The goal is to characterize the inner edge of the plasma sheet, so the focus is on large scale plasma sheet properties. Lower energy electron populations are ignored as they appear to be small-scale transients. Maxwellian, kappa and power-law distributed spectra are considered. Non-thermal ion distributions appear with greater frequency than anticipated. In order to be thermally distributed the differential energy flux must rise with a slope of ~2 toward a peak, after which the flux should fall sharply. The figure shows an apparently non-thermal ion distribution, together with a Maxwellian fit. The results from fits for one full year are presented.

  16. Clean Cities Fact Sheet

    SciTech Connect

    Not Available

    2004-01-01

    This fact sheet explains the Clean Cities Program and provides contact information for all coalitions and regional offices. It answers key questions such as: What is the Clean Cities Program? What are alternative fuels? How does the Clean Cities Program work? What sort of assistance does Clean Cities offer? What has Clean Cities accomplished? What is Clean Cities International? and Where can I find more information?

  17. Topographical atlas sheets

    USGS Publications Warehouse

    Wheeler, George Montague

    1876-01-01

    The following topographical atlas sheets, accompanying Appendix J.J. of the Annual Report of the Chief of Engineers, U.S. Army-being Annual Report upon U. S. Geographical Surveys-have been published during the fiscal year ending June 30, 1876, and are a portion of the series projected to embrace the territory of the United States lying west of the 100th meridian.

  18. Biomolecular Science (Fact Sheet)

    SciTech Connect

    Not Available

    2012-04-01

    A brief fact sheet about NREL Photobiology and Biomolecular Science. The research goal of NREL's Biomolecular Science is to enable cost-competitive advanced lignocellulosic biofuels production by understanding the science critical for overcoming biomass recalcitrance and developing new product and product intermediate pathways. NREL's Photobiology focuses on understanding the capture of solar energy in photosynthetic systems and its use in converting carbon dioxide and water directly into hydrogen and advanced biofuels.

  19. Latent TGF-[beta] structure and activation

    SciTech Connect

    Shi, Minlong; Zhu, Jianghai; Wang, Rui; Chen, Xing; Mi, Lizhi; Walz, Thomas; Springer, Timothy A.

    2011-09-16

    Transforming growth factor (TGF)-{beta} is stored in the extracellular matrix as a latent complex with its prodomain. Activation of TGF-{beta}1 requires the binding of {alpha}v integrin to an RGD sequence in the prodomain and exertion of force on this domain, which is held in the extracellular matrix by latent TGF-{beta} binding proteins. Crystals of dimeric porcine proTGF-{beta}1 reveal a ring-shaped complex, a novel fold for the prodomain, and show how the prodomain shields the growth factor from recognition by receptors and alters its conformation. Complex formation between {alpha}v{beta}6 integrin and the prodomain is insufficient for TGF-{beta}1 release. Force-dependent activation requires unfastening of a 'straitjacket' that encircles each growth-factor monomer at a position that can be locked by a disulphide bond. Sequences of all 33 TGF-{beta} family members indicate a similar prodomain fold. The structure provides insights into the regulation of a family of growth and differentiation factors of fundamental importance in morphogenesis and homeostasis.

  20. Luminescence Chronology for the Formation of Glacial Lake Calgary, Southern Alberta, Canada: Age Constraints for the Initiation of the Late Pleistocene Retreat of the Laurentide Ice Sheet from its Western Margin

    NASA Astrophysics Data System (ADS)

    Munyikwa, K.; Rittenour, T. M.

    2014-12-01

    Glacial Lake Calgary in southern Alberta, Canada, was a Late Pleistocene proglacial lake that formed along the southwest margin of the Laurentide Ice Sheet (LIS), dammed by the retreating ice sheet margin. Attempts to constrain the age of the lake using radiocarbon methods have been hampered by the lack of datable organic material. In an effort to apply an alternative chronometer, this study uses two optically stimulated luminescence (OSL) dating approaches to date fine grained sand and silt that were deposited in the lake during its existence. OSL dating determines the depositional ages of sediments by measuring the energy from ionizing radiation that is stored in mineral grains such as quartz and feldspar. Dividing the stored energy, also referred to as the paleodose, by the rate at which the dose accumulated, allows an age to be ascertained. In one method applied in this study, the paleodose stored in the feldspar component of the sediment is determined using normalized infrared stimulated luminescence signals acquired using a portable OSL reader. In the second method, blue optically stimulated luminescence signals obtained from quartz separates from the sediment by employing a regular OSL reader and standard protocols are used to determine the paleodose. After correcting the feldspar data for anomalous fading, the age results from the two dating approaches are compared. The ages signify a time period by which the LIS had retreated from the study area and, hence, serve as constraints for the initiation of the retreat of the ice sheet from its western limit. Advantages and limitations of the dating methods are briefly discussed. Constraining the chronology of the retreat of the LIS from western Canada allows for a better understanding of the driving forces behind ice sheet retreat. Secondly, assigning a temporal scale to the postglacial evolution of the environment of the region permits a better insight into the dynamics of the physical and biological

  1. Nuclear Data Sheets for A = 81

    SciTech Connect

    Baglin, Coral M.

    2008-10-15

    Nuclear structure data pertaining to all nuclei with mass number A = 81 (Zn, Ga, Ge, As, Se, Br, Kr, Rb, Sr, Y, Zr, Nb) have been compiled and evaluated and incorporated into the ENSDF data file. This publication for A = 81 supersedes the previous publication (Coral M. Baglin, Nuclear Data Sheets79, 447 (1996), literature cutoff 1 November 1996) and the subsequent updates by C. Baglin for {sup 81}Y (literature cutoff 8 October 1998) and {sup 81}Zr (literature cutoff 24 March 2000). All literature available prior to 15 August 2008 has been considered. Subsequent to previous A = 81 evaluations, excited states have been reported for the first time in {sup 81}Ga, and knowledge of excited state properties for {sup 81}Y and {sup 81}Zr has been significantly expanded. However, the expected {epsilon}+{beta}{sup +} decay of {sup 81}Zr has yet to be studied.

  2. Experimental realization of two-dimensional boron sheets.

    PubMed

    Feng, Baojie; Zhang, Jin; Zhong, Qing; Li, Wenbin; Li, Shuai; Li, Hui; Cheng, Peng; Meng, Sheng; Chen, Lan; Wu, Kehui

    2016-06-01

    A variety of two-dimensional materials have been reported in recent years, yet single-element systems such as graphene and black phosphorus have remained rare. Boron analogues have been predicted, as boron atoms possess a short covalent radius and the flexibility to adopt sp(2) hybridization, features that favour the formation of two-dimensional allotropes, and one example of such a borophene material has been reported recently. Here, we present a parallel experimental work showing that two-dimensional boron sheets can be grown epitaxially on a Ag(111) substrate. Two types of boron sheet, a β12 sheet and a χ3 sheet, both exhibiting a triangular lattice but with different arrangements of periodic holes, are observed by scanning tunnelling microscopy. Density functional theory simulations agree well with experiments, and indicate that both sheets are planar without obvious vertical undulations. The boron sheets are quite inert to oxidization and interact only weakly with their substrate. We envisage that such boron sheets may find applications in electronic devices in the future. PMID:27219700

  3. Eruptive Current Sheets Trailing SOHO/LASCO CMEs

    NASA Astrophysics Data System (ADS)

    Webb, David F.

    2015-04-01

    Current sheets are important signatures of magnetic reconnection during the eruption of solar magnetic structures. Many models of eruptive flare/Coronal Mass Ejections (CMEs) involve formation of a current sheet connecting the ejecting CME flux rope with the post-eruption magnetic loop arcade. Current sheets have been interpreted in white light images as narrow rays trailing the outward-moving CME, in ultraviolet spectra as narrow, bright hot features, and with different manifestations in other wavebands. This study continues that of Webb et al. (2003), who analyzed SMM white light CMEs having candidate magnetic disconnection features at the base of the CME. About half of those were followed by coaxial, bright rays suggestive of newly formed current sheets, and Webb et al. (2003) presented detailed results of analysis of those structures. In this work we extend the study of white light eruptive current sheets to the more sensitive and extensive SOHO/LASCO coronagraph data on CMEs. We comprehensively examined all LASCO CMEs during two periods that we identify with the minimum and maximum activity of solar cycle 23. We identified ~130 ray/current sheets during these periods, nearly all of which trailed CMEs with concave-outward backs. The occurrence rate of the ray/current sheets is 6-7% of all CMEs, irrespective of the solar cycle. We analyze the rays for durations, speeds, alignments, and motions and compare the observational results with some model predictions.

  4. Experimental realization of two-dimensional boron sheets

    NASA Astrophysics Data System (ADS)

    Feng, Baojie; Zhang, Jin; Zhong, Qing; Li, Wenbin; Li, Shuai; Li, Hui; Cheng, Peng; Meng, Sheng; Chen, Lan; Wu, Kehui

    2016-06-01

    A variety of two-dimensional materials have been reported in recent years, yet single-element systems such as graphene and black phosphorus have remained rare. Boron analogues have been predicted, as boron atoms possess a short covalent radius and the flexibility to adopt sp2 hybridization, features that favour the formation of two-dimensional allotropes, and one example of such a borophene material has been reported recently. Here, we present a parallel experimental work showing that two-dimensional boron sheets can be grown epitaxially on a Ag(111) substrate. Two types of boron sheet, a β12 sheet and a χ3 sheet, both exhibiting a triangular lattice but with different arrangements of periodic holes, are observed by scanning tunnelling microscopy. Density functional theory simulations agree well with experiments, and indicate that both sheets are planar without obvious vertical undulations. The boron sheets are quite inert to oxidization and interact only weakly with their substrate. We envisage that such boron sheets may find applications in electronic devices in the future.

  5. Dynamics of charged current sheets at high-latitude magnetopause

    NASA Astrophysics Data System (ADS)

    Savin, S.; Amata, E.; Zelenyi, L.; Dunlop, M.; Andre, M.; Song, P.; Blecki, J.; Buechner, J.; Rauch, J. L.; Skalsky, A.

    E. Amata (2), L. Zelenyi (1), M. Dunlop (3), M. Andre (4), P. Song (5), J. Blecki (6), J. Buechner (7), J.L Rauch, J.G. Trotignon (8), G. Consolini, F. Marcucci (2), B. Nikutowski (7), A. Skalsky, S. Romanov, E. Panov (1) (2) IFSI, Roma, Italy, (3) RAL, UK, (4) IRFU, Uppsala, Sweden, (5) U. Mass. Lowell, USA, (6) SRC, Warsaw, Poland, (7) MPAe, Germany, (8) LPCE, Orleans, France; We study dynamics of thin current sheets over polar cusps from data of Interball-1 and Cluster. At the high-beta magnetopause current sheet width often reaches ion gyroradius scales, that leads to their Hall dynamics in the presence of local surface charges. Respective perpendicular electric fields provide the means for momentum coupling through the current sheets and are able to accelerate ions with gyroradius of the order or larger than the sheet width. At borders of large diamagnetic cavities this mechanism is able to support mass exchange and accelerate/ heat incoming magnetosheath particles. At larger scales the inhomogeneous electric fields at the current sheet borders can accelerate incident plasma downtail along magnetopause via inertial drift. It serves to move external plasma away for dynamic equilibrium supporting. Farther away from magnetopause similar nonlinear electric field wave trains, selfconsistently produced by interaction of reflected from the obstacle waves with magnetosheath fluctuations, destroy the incident flux into accelerated magnetosonic jets and decelerated Alfvenic flows and generate small-scale current sheets due to different sign of electron and ion inertial drift in the nonlinear electric field bursts. We suggest that this direct kinetic energy transformation creates current sheets with anomalous statistics of field rotation angles in the turbulent boundary layer in front of magnetopause, which have been attributed earlier to an intermittent turbulence. We compare measured spectra with a model of nonlinear system with intermittent chaotic behavior. Work was

  6. Asymmetric Magnetic Reconnection in Coronal Mass Ejection Current Sheets

    NASA Astrophysics Data System (ADS)

    Pope, Crystal; Miralles, M. P.; Murphy, N. A.

    2012-01-01

    Flux rope models of coronal mass ejections (CMEs) predict the formation ofan elongated current sheet in the wake behind the rising plasmoid. These current sheets have been seen to drift or tilt over time by instruments including SOHO/LASCO and Hinode/XRT. We measure this in multiple observations including the 2008 April 9 "Cartwheel CME" and find an average drift that is far more than can be accounted for via the effects of solar rotation. The observed drift could be due to different parts of the current sheet actively reconnecting at different times (e.g., Savage et al. 2010), macroscopic effects from the rising flux rope pulling the plasma sheet along with it, or asymmetry in the magnetic reconnection process itself. These drift rates are compared with resistive magnetohydrodynamic (MHD) simulations of line-tied reconnection between magnetic fields of different strengths. The observed drift rates are comparable to predictions made by the simulations.

  7. Looking for a generic inhibitor of amyloid-like fibril formation among flavone derivatives

    PubMed Central

    Šneideris, Tomas; Baranauskienė, Lina; Cannon, Jonathan G.; Rutkienė, Rasa; Meškys, Rolandas

    2015-01-01

    A range of diseases is associated with amyloid fibril formation. Despite different proteins being responsible for each disease, all of them share similar features including beta-sheet-rich secondary structure and fibril-like protein aggregates. A number of proteins can form amyloid-like fibrils in vitro, resembling structural features of disease-related amyloids. Given these generic structural properties of amyloid and amyloid-like fibrils, generic inhibitors of fibril formation would be of interest for treatment of amyloid diseases. Recently, we identified five outstanding inhibitors of insulin amyloid-like fibril formation among the pool of 265 commercially available flavone derivatives. Here we report testing of these five compounds and of epi-gallocatechine-3-gallate (EGCG) on aggregation of alpha-synuclein and beta-amyloid. We used a Thioflavin T (ThT) fluorescence assay, relying on halftimes of aggregation as the measure of inhibition. This method avoids large numbers of false positive results. Our data indicate that four of the five flavones and EGCG inhibit alpha-synuclein aggregation in a concentration-dependent manner. However none of these derivatives were able to increase halftimes of aggregation of beta-amyloid. PMID:26421240

  8. The crystal structure of TGF-beta 3 and comparison to TGF-beta 2: implications for receptor binding.

    PubMed Central

    Mittl, P. R.; Priestle, J. P.; Cox, D. A.; McMaster, G.; Cerletti, N.; Grütter, M. G.

    1996-01-01

    Transforming growth factors beta belong to a group of cytokines that control cellular proliferation and differentiation. Five isoforms are known that share approximately 75% sequence identity, but exert different biological activities. The structure of TGF-beta 3 was solved by X-ray crystallography and refined to a final R-factor of 17.5% at 2.0 A resolution. Comparison with the structure of TGF-beta 2 (Schlunegger MP, Grütter MG, 1992, Nature 358:430-434; Daopin S, Piez KA, Ogawa Y, Davies DR, 1992, Science 257:369-373) reveals a virtually identical central core. Differences exist in the conformations of the N-terminal alpha-helix and in the beta-sheet loops. In TGF-beta 3, the N-terminal alpha-helix has moved approximately 1 A away from the central core. This movement can be correlated with the mutation of Leu 17 to Val and Ala 47 to Pro in TGF-beta 3. The beta-sheet loops rotate as a rigid body 9 degrees around an axis that runs approximately parallel to the dimer axis. If these differences are recognized by the TGF-beta receptors, they might account for the individual cellular responses. A molecule of the precipitating agent dioxane is bound in a crystal contact, forming a hydrogen bond with Trp 32. This dioxane may occupy a carbohydrate-binding site, because dioxane possesses some structural similarity with a carbohydrate. The dioxane is in contact with two tryptophans, which are often involved in carbohydrate recognition. PMID:8819159

  9. Identification of beta,beta-turns and unordered conformations in polypeptide chains by vacuum ultraviolet circular dichroism.

    PubMed

    Brahms, S; Brahms, J; Spach, G; Brack, A

    1977-08-01

    Different conformations of polypeptides were characterized by measurements of the circular dichroism (CD) extended into the vacuum ultraviolet region. (i) The linear beta-pleated sheet structure was characterized in a broad ultraviolet region down to 165 nm by examination of copolypeptides composed of alternating hydrophobic and hydrophilic amino-acid residues, e.g., poly(Lys-Leu-Lys-Leu). A short-wavelength intense band was found at about 169 nm, which is characteristic of beta-pleated sheet conformation. (ii) The beta-turns were experimentally measured using poly(Ala(2)-Gly(2)) in a broad spectral region down to 165 nm with accuracy. The observed CD spectrum is in excellent qualitative agreement with the theoretical curve calculated by Woody for the beta-turns of type II and/or I of Venkatachalam. The similarity in shape between the theoretical curve and the observed CD spectra suggests a dominance of beta-turn segments in the poly(Ala(2)-Gly(2)) structure. The presence of beta-turns in poly(Ala(2)-Gly(2)) is also in agreement with the characterization of this polypeptide by solid state methods (electron microscopy and x-ray diffraction). The CD spectrum of beta-turns is characterized by a very intense band at 207.5 nm and strong negative bands at 191 and 169 nm. Copolypeptides such as poly(Ala(2)-Gly(3)) and poly(Ala(3)-Gly(3)) yielded a similar type of CD spectrum, analysis of which indicates that a large fraction of their residues is contained in beta-turn regions. (iii) The CD spectrum of the unordered chain of these alternating copolypeptides in salt-free solution is observed in the vacuum ultraviolet region.

  10. Arachidonic acid mediates the formation of abundant alpha-helical multimers of alpha-synuclein

    NASA Astrophysics Data System (ADS)

    Iljina, Marija; Tosatto, Laura; Choi, Minee L.; Sang, Jason C.; Ye, Yu; Hughes, Craig D.; Bryant, Clare E.; Gandhi, Sonia; Klenerman, David

    2016-09-01

    The protein alpha-synuclein (αS) self-assembles into toxic beta-sheet aggregates in Parkinson’s disease, while it is proposed that αS forms soluble alpha-helical multimers in healthy neurons. Here, we have made αS multimers in vitro using arachidonic acid (ARA), one of the most abundant fatty acids in the brain, and characterized them by a combination of bulk experiments and single-molecule Fӧrster resonance energy transfer (sm-FRET) measurements. The data suggest that ARA-induced oligomers are alpha-helical, resistant to fibril formation, more prone to disaggregation, enzymatic digestion and degradation by the 26S proteasome, and lead to lower neuronal damage and reduced activation of microglia compared to the oligomers formed in the absence of ARA. These multimers can be formed at physiologically-relevant concentrations, and pathological mutants of αS form less multimers than wild-type αS. Our work provides strong biophysical evidence for the formation of alpha-helical multimers of αS in the presence of a biologically relevant fatty acid, which may have a protective role with respect to the generation of beta-sheet toxic structures during αS fibrillation.

  11. Arachidonic acid mediates the formation of abundant alpha-helical multimers of alpha-synuclein

    PubMed Central

    Iljina, Marija; Tosatto, Laura; Choi, Minee L.; Sang, Jason C.; Ye, Yu; Hughes, Craig D.; Bryant, Clare E.; Gandhi, Sonia; Klenerman, David

    2016-01-01

    The protein alpha-synuclein (αS) self-assembles into toxic beta-sheet aggregates in Parkinson’s disease, while it is proposed that αS forms soluble alpha-helical multimers in healthy neurons. Here, we have made αS multimers in vitro using arachidonic acid (ARA), one of the most abundant fatty acids in the brain, and characterized them by a combination of bulk experiments and single-molecule Fӧrster resonance energy transfer (sm-FRET) measurements. The data suggest that ARA-induced oligomers are alpha-helical, resistant to fibril formation, more prone to disaggregation, enzymatic digestion and degradation by the 26S proteasome, and lead to lower neuronal damage and reduced activation of microglia compared to the oligomers formed in the absence of ARA. These multimers can be formed at physiologically-relevant concentrations, and pathological mutants of αS form less multimers than wild-type αS. Our work provides strong biophysical evidence for the formation of alpha-helical multimers of αS in the presence of a biologically relevant fatty acid, which may have a protective role with respect to the generation of beta-sheet toxic structures during αS fibrillation. PMID:27671749

  12. Synchrotron-based Infrared and X-ray Imaging Shows Focalized Accumulation of Cu and Zn Co-localized With Beta-amyloid Deposits in Alzheimer's Disease

    SciTech Connect

    Miller,L.; Wang, Q.; Telivala, T.; Smith, R.; Lanzirotti, A.; Miklossy, J.

    2006-01-01

    Alzheimer's disease (AD) is characterized by the misfolding and plaque-like accumulation of a naturally occurring peptide in the brain called amyloid beta (Abeta). Recently, this process has been associated with the binding of metal ions such as iron (Fe), copper (Cu), and zinc (Zn). It is thought that metal dyshomeostasis is involved in protein misfolding and may lead to oxidative stress and neuronal damage. However, the exact role of the misfolded proteins and metal ions in the degenerative process of AD is not yet clear. In this study, we used synchrotron Fourier transform infrared micro-spectroscopy (FTIRM) to image the in situ secondary structure of the amyloid plaques in brain tissue of AD patients. These results were spatially correlated with metal ion accumulation in the same tissue sample using synchrotron X-ray fluorescence (SXRF) microprobe. For both techniques, a spatial resolution of 5-10 microm was achieved. FTIRM results showed that the amyloid plaques have elevated beta-sheet content, as demonstrated by a strong amide I absorbance at 1625cm(-1). Using SXRF microprobe, we find that AD tissue also contains 'hot spots' of accumulated metal ions, specifically Cu and Zn, with a strong spatial correlation between these two ions. The 'hot spots' of accumulated Zn and Cu were co-localized with beta-amyloid plaques. Thus for the first time, a strong spatial correlation has been observed between elevated beta-sheet content in Abeta plaques and accumulated Cu and Zn ions, emphasizing an association of metal ions with amyloid formation in AD.

  13. A Single Mutation at the Sheet Switch Region Results in Conformational Changes Favoring 6 Light-Chain Fibrillogenesis

    SciTech Connect

    Hernández-Santoyo, A.; Del Pozo Yauner, L; Fuentes-Silva, D; Ortiz, E; Rudiño-Piñera, E; Sánchez-López, R; Horjales, E; Becerril, B; Rodríguez-Romero, A

    2010-01-01

    Systemic amyloid light-chain (LC) amyloidosis is a disease process characterized by the pathological deposition of monoclonal LCs in tissue. All LC subtypes are capable of fibril formation although {lambda} chains, particularly those belonging to the {lambda}6 type, are overrepresented. Here, we report the thermodynamic and in vitro fibrillogenic properties of several mutants of the {lambda}6 protein 6aJL2 in which Pro7 and/or His8 was substituted by Ser or Pro. The H8P and H8S mutants were almost as stable as the wild-type protein and were poorly fibrillogenic. In contrast, the P7S mutation decreased the thermodynamic stability of 6aJL2 and greatly enhanced its capacity to form amyloid-like fibrils in vitro. The crystal structure of the P7S mutant showed that the substitution induced both local and long-distance effects, such as the rearrangement of the VL (variable region of the light chain)-VL interface. This mutant crystallized in two orthorhombic polymorphs, P2{sub 1}2{sub 1}2{sub 1} and C222{sub 1}. In the latter, a monomer that was not arranged in the typical Bence-Jones dimer was observed for the first time. Crystal-packing analysis of the C222{sub 1} lattice showed the establishment of intermolecular {beta}-{beta} interactions that involved the N-terminus and {beta}-strand B and that these could be relevant in the mechanism of LC fibril formation. Our results strongly suggest that Pro7 is a key residue in the conformation of the N-terminal sheet switch motif and, through long-distance interactions, is also critically involved in the contacts that stabilized the VL interface in {lambda}6 LCs.

  14. High Beta Tokamaks

    SciTech Connect

    Cowley, S.

    1998-11-14

    Perhaps the ideal tokamak would have high {beta} ({beta} {approx}> 1) and classical confinement. Such a tokamak has not been found, and we do not know if one does exist. We have searched for such a possibility, so far without success. In 1990, we obtained analytic equilibrium solutions for large aspect ratio tokamaks at {beta} {approx} {Omicron}(1) [1]. These solutions and the extension at high {beta} poloidal to finite aspect ratio [2] provided a basis for the study of high {beta} tokamaks. We have shown that these configurations can be stable to short scale MHD modes [3], and that they have reduced neoclassical transport [4]. Microinstabilities (such as the {del}T{sub i} mode) seem to be stabilized at high {beta} [5] - this is due to the large local shear [3] and the magnetic well. We have some concerns about modes associated with the compressional branch which may appear at high {beta}. Bill Dorland and Mike Kotschenreuther have studied this issue and our concerns may be unfounded. It is certainly tantalizing, especially given the lowered neoclassical transport values, that these configurations could have no microinstabilities and, one could assume, no anomalous transport. Unfortunately, while this work is encouraging, the key question for high {beta} tokamaks is the stability to large scale kink modes. The MHD {beta} limit (Troyon limit) for kink modes at large aspect ratio is problematically low. There is ample evidence from computations that the limit exists. However, it is not known if stable equilibria exist at much higher {beta}--none have been found. We have explored this question in the asymptotic high {beta} poloidal limit. Unfortunately, we are unable to find stable equilibrium and also unable to show that they don't exist. The results of these calculations will be published when a more definitive answer is found.

  15. Immunolocalization of alpha-keratins and feather beta-proteins in feather cells and comparison with the general process of cornification in the skin of mammals.

    PubMed

    Alibardi, L

    2013-03-01

    The maturation of the corneous material of feathers is a special case of cornification in vertebrate epidermis and is believed to occur mainly by the accumulation of small proteins of about 100 amino acids and a central beta-pleated sheet region known as feather keratins. The present immunocytochemical study carried out using double-labeling immunogold shows that a small amount of alpha-keratins of intermediate filament type form the early keratin clumps in barb and barbule cells. These initial nuclei of formation of corneous material are rapidly coated by the deposition of large amounts of small feather keratin-associated beta-proteins (feather keratins). The latter proteins turn the keratin bundles of barb and barbule cells into a compact and apparently amorphous mass of corneous material where no sign of intermediate filaments are seen. Feather beta-proteins however form an irregular filamentous network of 2-3nm thick electron-pale filaments and produce the characteristic feather X-ray pattern due to their prevalent amount over any other protein present in feather cells. The modality of cornification in feathers is discussed in relation to the process of formation of corneous material in the skin of vertebrates in general that occurs by the association of intermediate filament proteins and keratin-associated proteins.

  16. Ice sheets and nitrogen.

    PubMed

    Wolff, Eric W

    2013-07-01

    Snow and ice play their most important role in the nitrogen cycle as a barrier to land-atmosphere and ocean-atmosphere exchanges that would otherwise occur. The inventory of nitrogen compounds in the polar ice sheets is approximately 260 Tg N, dominated by nitrate in the much larger Antarctic ice sheet. Ice cores help to inform us about the natural variability of the nitrogen cycle at global and regional scale, and about the extent of disturbance in recent decades. Nitrous oxide concentrations have risen about 20 per cent in the last 200 years and are now almost certainly higher than at any time in the last 800 000 years. Nitrate concentrations recorded in Greenland ice rose by a factor of 2-3, particularly between the 1950s and 1980s, reflecting a major change in NOx emissions reaching the background atmosphere. Increases in ice cores drilled at lower latitudes can be used to validate or constrain regional emission inventories. Background ammonium concentrations in Greenland ice show no significant recent trend, although the record is very noisy, being dominated by spikes of input from biomass burning events. Neither nitrate nor ammonium shows significant recent trends in Antarctica, although their natural variations are of biogeochemical and atmospheric chemical interest. Finally, it has been found that photolysis of nitrate in the snowpack leads to significant re-emissions of NOx that can strongly impact the regional atmosphere in snow-covered areas.

  17. Ice sheets and nitrogen

    PubMed Central

    Wolff, Eric W.

    2013-01-01

    Snow and ice play their most important role in the nitrogen cycle as a barrier to land–atmosphere and ocean–atmosphere exchanges that would otherwise occur. The inventory of nitrogen compounds in the polar ice sheets is approximately 260 Tg N, dominated by nitrate in the much larger Antarctic ice sheet. Ice cores help to inform us about the natural variability of the nitrogen cycle at global and regional scale, and about the extent of disturbance in recent decades. Nitrous oxide concentrations have risen about 20 per cent in the last 200 years and are now almost certainly higher than at any time in the last 800 000 years. Nitrate concentrations recorded in Greenland ice rose by a factor of 2–3, particularly between the 1950s and 1980s, reflecting a major change in NOx emissions reaching the background atmosphere. Increases in ice cores drilled at lower latitudes can be used to validate or constrain regional emission inventories. Background ammonium concentrations in Greenland ice show no significant recent trend, although the record is very noisy, being dominated by spikes of input from biomass burning events. Neither nitrate nor ammonium shows significant recent trends in Antarctica, although their natural variations are of biogeochemical and atmospheric chemical interest. Finally, it has been found that photolysis of nitrate in the snowpack leads to significant re-emissions of NOx that can strongly impact the regional atmosphere in snow-covered areas. PMID:23713125

  18. Twisting of sheet metals

    NASA Astrophysics Data System (ADS)

    Pham, C. H.; Thuillier, S.; Manach, P. Y.

    2013-12-01

    Twisting of metallic sheets is one particular mode of springback that occurs after drawing of elongated parts, i.e. with one dimension much larger than the two others. In this study, a dedicated device for drawing of elongated part with a U-shaped section has been designed on purpose, in order to obtain reproducible data. Very thin metallic sheet, of thickness 0.15 mm, has been used, so that the maximum length of the part is 100 mm. Two different orientations of the part with respect to the tools have been chosen: either aligned with the tools, or purposefully misaligned by 2°. Several samples were drawn for each configuration, leading to the conclusion that almost no twisting occurs in the first case whereas a significant one can be measured for the second one. In a second step, 2D and 3D numerical simulations within the implicit framework for drawing and springback were carried out. A mixed hardening law associated to von Mises yield criterion represents accurately the mechanical behavior of the material. This paper highlights a comparison of numerical predictions with experiments, e.g. the final shape of the part and the twisting parameter.

  19. Interstrand side chain--side chain interactions in a designed beta-hairpin: significance of both lateral and diagonal pairings.

    PubMed

    Syud, F A; Stanger, H E; Gellman, S H

    2001-09-12

    The contributions of interstrand side chain-side chain contacts to beta-sheet stability have been examined with an autonomously folding beta-hairpin model system. RYVEV(D)PGOKILQ-NH2 ((D)P = D-proline, O = ornithine) has previously been shown to adopt a beta-hairpin conformation in aqueous solution, with a two-residue loop at D-Pro-Gly. In the present study, side chains that display interstrand NOEs (Tyr-2, Lys-9, and Leu-11) are mutated to alanine or serine, and the conformational impact of the mutations is assessed. In the beta-hairpin conformation Tyr-2 and Leu-11 are directly across from one another (non-hydrogen bonded pair). This "lateral" juxtaposition of two hydrophobic side chains appears to contribute to beta-hairpin conformational stability, which is consistent with results from other beta-sheet model studies and with statistical analyses of interstrand residue contacts in protein crystal structures. Interaction between the side chains of Tyr-2 and Lys-9 also stabilizes the beta-hairpin conformation. Tyr-2/Lys-9 is a "diagonal" interstrand juxtaposition because these residues are not directly across from one another in terms of the hydrogen bonding registry between the strands. This diagonal interaction arises from the right-handed twist that is commonly observed among beta-sheets. Evidence of diagonal side chain-side chain contacts has been observed in other autonomously folding beta-sheet model systems, but we are not aware of other efforts to determine whether a diagonal interaction contributes to beta-sheet stability.

  20. Laminated sheet composites reinforced with modular filament sheet

    NASA Technical Reports Server (NTRS)

    Reece, O. Y.

    1968-01-01

    Aluminum and magnesium composite sheet laminates reinforced with low density, high strength modular filament sheets are produced by diffusion bonding and explosive bonding. Both processes are accomplished in normal atmosphere and require no special tooling or cleaning other than wire brushing the metal surfaces just prior to laminating.

  1. 13. Photograph of sheet 1 (index and title sheet) of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    13. Photograph of sheet 1 (index and title sheet) of the Indiana State Highway Commission repair plans of 1969 for the Cicott Street Bridge. Photograph of a 24' by 36' print made from microfilm in the archives of the Indiana Department of Transportation in Indianapolis. - Cicott Street Bridge, Spanning Wabash River at State Road 25, Logansport, Cass County, IN

  2. 9. Photograph of sheet 1 (index and title sheet) of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    9. Photograph of sheet 1 (index and title sheet) of the State Highway Department of Indiana repair plans of 1957 for the Cicott Street Bridge. Photograph of a 24' by 36' print made from microfilm in the archives of the Indiana Department of Transportation in Indianapolis. - Cicott Street Bridge, Spanning Wabash River at State Road 25, Logansport, Cass County, IN

  3. 17. INTAKE PIER, BRIDGE STRESS SHEET, SHEET 8 OF 117, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    17. INTAKE PIER, BRIDGE STRESS SHEET, SHEET 8 OF 117, 1920. - Sacramento River Water Treatment Plant Intake Pier & Access Bridge, Spanning Sacramento River approximately 175 feet west of eastern levee on river; roughly .5 mile downstream from confluence of Sacramento & American Rivers, Sacramento, Sacramento County, CA

  4. 10. KIDNER BRIDGE STRUCTURAL STEEL DETAIL SHEET (original plan sheet ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    10. KIDNER BRIDGE STRUCTURAL STEEL DETAIL SHEET (original plan sheet is in possession of Ball State University, Drawings and Documents Archive, COllege of Architecture and Planing, Ball State University, Muncie, Indiana, 47306 - Kidner Bridge, Spanning Mississinewa River at County Road 700 South, Upland, Grant County, IN

  5. Method for heating a glass sheet

    DOEpatents

    Boaz, Premakaran Tucker

    1998-01-01

    A method for heating a glass sheet includes the steps of heating a glass sheet to a first predetermined temperature and applying microwave energy to the glass sheet to heat the glass sheet to at least a second predetermined temperature to allow the glass sheet to be formed.

  6. Method for heating a glass sheet

    DOEpatents

    Boaz, P.T.

    1998-07-21

    A method for heating a glass sheet includes the steps of heating a glass sheet to a first predetermined temperature and applying microwave energy to the glass sheet to heat the glass sheet to at least a second predetermined temperature to allow the glass sheet to be formed. 5 figs.

  7. Modeling the formation of secondary organic aerosol. 1. Application of theoretical principles to measurements obtained in the alpha-pinene/, beta-pinene/, sabinene/, delta3-carene/, and cyclohexane/ozone systems.

    PubMed

    Pankow, J F; Seinfeld, J H; Asher, W E; Erdakos, G B

    2001-03-15

    , similarly low-volatility compounds. This was overcome in part by using the G/P data from the alpha-pinene and cyclohexene experiments to determine pL(degrees) values for use (along with a set of 14 other independent polar compounds) in calculating UNIFAC vapor pressure parameters that were, in turn, used to estimate all of the needed pL(degrees) values. The significant degree of resultant circularity in the calculations for alpha-pinene and cyclohexene helped lead to the good agreement that was found between the Yi values predicted by the model, and those measured experimentally for those two compounds. However, the model was also able to predict the aerosol yield values from beta-pinene, sabinene, and delta3-carene, for which there was significatly less circularity in the calculations, thereby providing evidence supporting the idea that given the correct input information, SOA formation can in fact be accurately modeled as a multicomponent condensation process.

  8. Dawn-dusk asymmetries in plasma sheet particle distributions and the average behaviour of magnetotail current systems

    NASA Astrophysics Data System (ADS)

    Walsh, A. P.; Forsyth, C.; Owen, C. J.; Fazakerley, A. N.; Dandouras, I. S.

    2011-12-01

    We present the results of a survey of Cluster PEACE and CIS-CODIF data taken in the 2001-2006 tail seasons, building on the work of Walsh et al. (GRL, 2011). We examine the average pitch angle distributions of protons and electrons in the magnetotail as a function of proton plasma beta, restricted to times when the magnetosphere was exposed to steady (on a 3 hour timescale) IMF conditions and focussing in particular on dawn-dusk asymmetries. We confirm that, on average, the 2 component proton plasma sheet exists duskward of the noon-midnight meridian under steady northward IMF. An associated population of cold electrons is also observed. Dawnward of the noon-midnight meridian there are no significant fluxes of the cold component of protons and much reduced fluxes of the cold electron component, implying transport across the dusk magnetopause is the dominant formation mechanism of the two component plasma sheet for both protons and electrons. Under southward IMF, dawn-dusk asymmetries in the protons are controlled by the Y component of the IMF. For the electrons higher fluxes of high energy, field-aligned, particles are observed at dusk than at dawn. This suggests a link to a duskward offset of the tail neutral line and the preferential observation of substorm-related tail signatures in the premidnight sector. We also consider the relationship between the observed particle populations and the average behaviour of the large-scale magnetotail current systems as revealed by the Curlometer.

  9. On the origin of the beta cell.

    PubMed

    Oliver-Krasinski, Jennifer M; Stoffers, Doris A

    2008-08-01

    The major forms of diabetes are characterized by pancreatic islet beta-cell dysfunction and decreased beta-cell numbers, raising hope for cell replacement therapy. Although human islet transplantation is a cell-based therapy under clinical investigation for the treatment of type 1 diabetes, the limited availability of human cadaveric islets for transplantation will preclude its widespread therapeutic application. The result has been an intense focus on the development of alternate sources of beta cells, such as through the guided differentiation of stem or precursor cell populations or the transdifferentiation of more plentiful mature cell populations. Realizing the potential for cell-based therapies, however, requires a thorough understanding of pancreas development and beta-cell formation. Pancreas development is coordinated by a complex interplay of signaling pathways and transcription factors that determine early pancreatic specification as well as the later differentiation of exocrine and endocrine lineages. This review describes the current knowledge of these factors as they relate specifically to the emergence of endocrine beta cells from pancreatic endoderm. Current therapeutic efforts to generate insulin-producing beta-like cells from embryonic stem cells have already capitalized on recent advances in our understanding of the embryonic signals and transcription factors that dictate lineage specification and will most certainly be further enhanced by a continuing emphasis on the identification of novel factors and regulatory relationships. PMID:18676806

  10. [Clip Sheets from BOCES. Opportunities. Health. Careers. = Oportunidades. Salud. Una Camera En...

    ERIC Educational Resources Information Center

    State Univ. of New York, Geneseo. Coll. at Geneseo. Migrant Center.

    This collection of 83 clip sheets, or classroom handouts, was created to help U.S. migrants learn more about health, careers, and general "opportunities" including education programs. They are written in both English and Spanish and are presented in an easily understandable format. Health clip-sheet topics include the following: Abuse; AIDS;…

  11. Amino Acid Distribution Rules Predict Protein Fold: Protein Grammar for Beta-Strand Sandwich-Like Structures

    PubMed Central

    Kister, Alexander

    2015-01-01

    We present an alternative approach to protein 3D folding prediction based on determination of rules that specify distribution of “favorable” residues, that are mainly responsible for a given fold formation, and “unfavorable” residues, that are incompatible with that fold, in polypeptide sequences. The process of determining favorable and unfavorable residues is iterative. The starting assumptions are based on the general principles of protein structure formation as well as structural features peculiar to a protein fold under investigation. The initial assumptions are tested one-by-one for a set of all known proteins with a given structure. The assumption is accepted as a “rule of amino acid distribution” for the protein fold if it holds true for all, or near all, structures. If the assumption is not accepted as a rule, it can be modified to better fit the data and then tested again in the next step of the iterative search algorithm, or rejected. We determined the set of amino acid distribution rules for a large group of beta sandwich-like proteins characterized by a specific arrangement of strands in two beta sheets. It was shown that this set of rules is highly sensitive (~90%) and very specific (~99%) for identifying sequences of proteins with specified beta sandwich fold structure. The advantage of the proposed approach is that it does not require that query proteins have a high degree of homology to proteins with known structure. So long as the query protein satisfies residue distribution rules, it can be confidently assigned to its respective protein fold. Another advantage of our approach is that it allows for a better understanding of which residues play an essential role in protein fold formation. It may, therefore, facilitate rational protein engineering design. PMID:25625198

  12. Active volcanism beneath the West Antarctic ice sheet and implications for ice-sheet stability

    USGS Publications Warehouse

    Blankenship, D.D.; Bell, R.E.; Hodge, S.M.; Brozena, J.M.; Behrendt, John C.; Finn, C.A.

    1993-01-01

    IT is widely understood that the collapse of the West Antarctic ice sheet (WAIS) would cause a global sea level rise of 6 m, yet there continues to be considerable debate about the detailed response of this ice sheet to climate change1-3. Because its bed is grounded well below sea level, the stability of the WAIS may depend on geologically controlled conditions at the base which are independent of climate. In particular, heat supplied to the base of the ice sheet could increase basal melting and thereby trigger ice streaming, by providing the water for a lubricating basal layer of till on which ice streams are thought to slide4,5. Ice streams act to protect the reservoir of slowly moving inland ice from exposure to oceanic degradation, thus enhancing ice-sheet stability. Here we present aerogeophysical evidence for active volcanism and associated elevated heat flow beneath the WAIS near the critical region where ice streaming begins. If this heat flow is indeed controlling ice-stream formation, then penetration of ocean waters inland of the thin hot crust of the active portion of the West Antarctic rift system could lead to the disappearance of ice streams, and possibly trigger a collapse of the inland ice reservoir.

  13. The Rapid Ice Sheet Change Observatory (RISCO)

    NASA Astrophysics Data System (ADS)

    Morin, P.; Howat, I. M.; Ahn, Y.; Porter, C.; McFadden, E. M.

    2010-12-01

    The recent expansion of observational capacity from space has revealed dramatic, rapid changes in the Earth’s ice cover. These discoveries have fundamentally altered how scientists view ice-sheet change. Instead of just slow changes in snow accumulation and melting over centuries or millennia, important changes can occur in sudden events lasting only months, weeks, or even a single day. Our understanding of these short time- and space-scale processes, which hold important implications for future global sea level rise, has been impeded by the low temporal and spatial resolution, delayed sensor tasking, incomplete coverage, inaccessibility and/or high cost of data available to investigators. New cross-agency partnerships and data access policies provide the opportunity to dramatically improve the resolution of ice sheet observations by an order of magnitude, from timescales of months and distances of 10’s of meters, to days and meters or less. Advances in image processing technology also enable application of currently under-utilized datasets. The infrastructure for systematically gathering, processing, analyzing and distributing these data does not currently exist. Here we present the development of a multi-institutional, multi-platform observatory for rapid ice change with the ultimate objective of helping to elucidate the relevant timescales and processes of ice sheet dynamics and response to climate change. The Rapid Ice Sheet Observatory (RISCO) gathers observations of short time- and space-scale Cryosphere events and makes them easily accessible to investigators, media and general public. As opposed to existing data centers, which are structured to archive and distribute diverse types of raw data to end users with the specialized software and skills to analyze them, RISCO focuses on three types of geo-referenced raster (image) data products in a format immediately viewable with commonly available software. These three products are (1) sequences of images

  14. Current sheet thinning, reconnection onset, and auroral morphology during geomagnetic substorms

    NASA Astrophysics Data System (ADS)

    Otto, A.; Hsieh, M. S.

    2015-12-01

    Geomagnetic substorms represent a fundamental energy release mechanism for the terrestrial magnetosphere. Specifically, the evolution of thin currents sheets during the substorm growth phase plays a key role for substorms because such current sheets present a much lower threshold for the onset of tearing modes and magnetic reconnection than the usually thick magnetotail current sheet. Here we examine and compare two basic processes for current sheet thinning in the Earth's magnetotail: Current sheet thinning (1) through closed magnetic flux depletion (MFD) in the near Earth magnetotail caused by divergent flux transport to replace closed flux on the dayside and (2) through accumulation of open flux magnetic flux in the tail lobes also caused by dayside reconnection. Both processes are expected to operate during any period of enhanced dayside reconnection. It is demonstrated that closed magnetic flux depletion (MFD) in the near Earth magnetotail and the increase of open lobe magnetic flux can lead to the evolution of two separate thin current sheets in the near Earth and the mid tail regions of the magnetosphere. While the auroral morphology associated with MFD and near Earth current sheet formation is well consistent with typical substorm growth observation, midtail current sheet formation through lobe flux increase shows only a minor influence on the auroral ionosphere. We discuss the physics of the dual current sheet formation and local and auroral properties of magnetic reconnection in either current sheet. It is suggested that only reconnection onset in the near Earth current sheet may be consistent with substorm expansion because the flux tube entropy depletion of mid tail reconnection appears insufficient to cause geosynchronous particle injection and dipolarization. Therefore reconnection in the mid tail current sheet is more likely associated with bursty bulk flows or dipolarization fronts which stop short of geosynchronous distances.

  15. Rapid synthesis of beta zeolites

    SciTech Connect

    Fan, Wei; Chang, Chun -Chih; Dornath, Paul; Wang, Zhuopeng

    2015-08-18

    The invention provides methods for rapidly synthesizing heteroatom containing zeolites including Sn-Beta, Si-Beta, Ti-Beta, Zr-Beta and Fe-Beta. The methods for synthesizing heteroatom zeolites include using well-crystalline zeolite crystals as seeds and using a fluoride-free, caustic medium in a seeded dry-gel conversion method. The Beta zeolite catalysts made by the methods of the invention catalyze both isomerization and dehydration reactions.

  16. Vertically scanned laser sheet microscopy.

    PubMed

    Dong, Di; Arranz, Alicia; Zhu, Shouping; Yang, Yujie; Shi, Liangliang; Wang, Jun; Shen, Chen; Tian, Jie; Ripoll, Jorge

    2014-01-01

    Laser sheet microscopy is a widely used imaging technique for imaging the three-dimensional distribution of a fluorescence signal in fixed tissue or small organisms. In laser sheet microscopy, the stripe artifacts caused by high absorption or high scattering structures are very common, greatly affecting image quality. To solve this problem, we report here a two-step procedure which consists of continuously acquiring laser sheet images while vertically displacing the sample, and then using the variational stationary noise remover (VSNR) method to further reduce the remaining stripes. Images from a cleared murine colon acquired with a vertical scan are compared with common stitching procedures demonstrating that vertically scanned light sheet microscopy greatly improves the performance of current light sheet microscopy approaches without the need for complex changes to the imaging setup and allows imaging of elongated samples, extending the field of view in the vertical direction.

  17. Hyperspectral light sheet microscopy.

    PubMed

    Jahr, Wiebke; Schmid, Benjamin; Schmied, Christopher; Fahrbach, Florian O; Huisken, Jan

    2015-01-01

    To study the development and interactions of cells and tissues, multiple fluorescent markers need to be imaged efficiently in a single living organism. Instead of acquiring individual colours sequentially with filters, we created a platform based on line-scanning light sheet microscopy to record the entire spectrum for each pixel in a three-dimensional volume. We evaluated data sets with varying spectral sampling and determined the optimal channel width to be around 5 nm. With the help of these data sets, we show that our setup outperforms filter-based approaches with regard to image quality and discrimination of fluorophores. By spectral unmixing we resolved overlapping fluorophores with up to nanometre resolution and removed autofluorescence in zebrafish and fruit fly embryos. PMID:26329685

  18. Hyperspectral light sheet microscopy

    NASA Astrophysics Data System (ADS)

    Jahr, Wiebke; Schmid, Benjamin; Schmied, Christopher; Fahrbach, Florian O.; Huisken, Jan

    2015-09-01

    To study the development and interactions of cells and tissues, multiple fluorescent markers need to be imaged efficiently in a single living organism. Instead of acquiring individual colours sequentially with filters, we created a platform based on line-scanning light sheet microscopy to record the entire spectrum for each pixel in a three-dimensional volume. We evaluated data sets with varying spectral sampling and determined the optimal channel width to be around 5 nm. With the help of these data sets, we show that our setup outperforms filter-based approaches with regard to image quality and discrimination of fluorophores. By spectral unmixing we resolved overlapping fluorophores with up to nanometre resolution and removed autofluorescence in zebrafish and fruit fly embryos.

  19. Hyperspectral light sheet microscopy

    PubMed Central

    Jahr, Wiebke; Schmid, Benjamin; Schmied, Christopher; Fahrbach, Florian O.; Huisken, Jan

    2015-01-01

    To study the development and interactions of cells and tissues, multiple fluorescent markers need to be imaged efficiently in a single living organism. Instead of acquiring individual colours sequentially with filters, we created a platform based on line-scanning light sheet microscopy to record the entire spectrum for each pixel in a three-dimensional volume. We evaluated data sets with varying spectral sampling and determined the optimal channel width to be around 5 nm. With the help of these data sets, we show that our setup outperforms filter-based approaches with regard to image quality and discrimination of fluorophores. By spectral unmixing we resolved overlapping fluorophores with up to nanometre resolution and removed autofluorescence in zebrafish and fruit fly embryos. PMID:26329685

  20. Vitamin and Mineral Supplement Fact Sheets

    MedlinePlus

    ... Tables Online DRI Tool Daily Value (DV) Tables Vitamin and Mineral Supplement Fact Sheets Search the list ... Supplements: Background Information Botanical Dietary Supplements: Background Information Vitamin and Mineral Fact Sheets Botanical Supplement Fact Sheets ...

  1. West Antarctic Ice Sheet formed earlier than thought

    NASA Astrophysics Data System (ADS)

    Balcerak, Ernie

    2013-10-01

    About 34 million years ago, Earth transitioned from a warm "greenhouse" climate to a cold "icehouse" climate, marking the transition between the Eocene and Oligocene epochs. This transition has been associated with the formation of a large ice sheet on Antarctica.

  2. Writing by Number: Teaching Students to Read the Balance Sheet.

    ERIC Educational Resources Information Center

    Cross, Mary

    1990-01-01

    Describes an assignment in which students write a short memo report analyzing and comparing both what a company says in its annual report and what its balance sheet shows. Describes four simple mathematical formulas students can use to quickly diagnose a company's financial health. Appends a sample of the short report format. (RS)

  3. Tyrosine residues 654 and 670 in {beta}-cat enin are crucial in regulation of Met-{beta}-catenin interactions

    SciTech Connect

    Zeng, Gang; Apte, Udayan; Micsenyi, Amanda; Bell, Aaron; Monga, Satdarshan P.S. . E-mail: smonga@pitt.edu

    2006-11-01

    {beta}-catenin, a key component of the canonical Wnt pathway, is also regulated by tyrosine phosphorylation that regulates its association to E-cadherin. Previously, we reported its association with the hepatocyte growth factor (HGF) receptor Met at the membrane. HGF induced Met-{beta}-catenin dissociation and nuclear translocation of {beta}-catenin, which was tyrosine-phosphorylation-dependent. Here, we further investigate the Met-{beta}-catenin interaction by selectively mutating several tyrosine residues, alone or in combination, in {beta}-catenin. The mutants were subcloned into FLAG-CMV vector and stably transfected into rat hepatoma cells, which were treated with HGF. All single or double-mutant-transfected cells continued to show HGF-induced nuclear translocation of FLAG-{beta}-catenin except the mutations affecting 654 and 670 simultaneously (Y654/670F), which coincided with the lack of formation of {beta}-catenin-TCF complex and DNA synthesis, in response to the HGF treatment. In addition, the Y654/670F-transfected cells also showed no phosphorylation of {beta}-catenin or dissociation from Met in response to HGF. Thus, intact 654 and 670 tyrosine residues in {beta}-catenin are crucial in HGF-mediated {beta}-catenin translocation, activation and mitogenesis.

  4. A fluorescent assay amenable to measuring production of beta-D-glucuronides produced from recombinant UDP-glycosyl transferase enzymes.

    PubMed

    Trubetskoy, O V; Shaw, P M

    1999-05-01

    Beta-glucuronidase cleavage of 4-methylumbelliferyl beta-D-glucuronide generates the highly fluorescent compound, 4-methylumbelliferone. We show that other beta-D-glucuronide compounds act as competitors in this assay. The 4-methylumbelliferyl beta-D-glucuronide cleavage assay can easily be adapted to high throughput formats to detect the presence of beta-D glucuronides generated using recombinant glycosyl transferase preparations.

  5. Penguin Fact Sheet.

    ERIC Educational Resources Information Center

    Flotsam and Jetsam: A Newsletter for Massachusetts Marine Educators, 1985

    1985-01-01

    Presents factual information on penguins using an outline format. Includes descriptions of physical characteristics, behavioral mechanisms, geographical distribution, and physiological processes. Provides separate bibliographies for teachers and students. (ML)

  6. Current Sheet Properties and Dynamics During Sympathetic Breakout Eruptions

    NASA Astrophysics Data System (ADS)

    Lynch, B. J.; Edmondson, J. K.

    2013-12-01

    We present the continued analysis of the high-resolution 2.5D MHD simulations of sympathetic magnetic breakout eruptions from a pseudostreamer source region. We examine the generation of X- and O-type null points during the current sheet tearing and track the magnetic island formation and evolution during periods of reconnection. The magnetic breakout eruption scenario forms an overlying 'breakout' current sheet that evolves slowly and removes restraining flux from above the sheared field core that will eventually become the center of the erupting flux rope-like structure. The runaway expansion from the expansion-breakout reconnection positive feedback enables the formation of the second, vertical/radial current sheet underneath the rising sheared field core as in the standard CHSKP eruptive flare scenario. We will examine the flux transfer rates through the breakout and flare current sheets and compare the properties of the field and plasma inflows into the current sheets and the reconnection jet outflows into the flare loops and flux rope ejecta.

  7. {alpha}-Lipoic acid exhibits anti-amyloidogenicity for {beta}-amyloid fibrils in vitro

    SciTech Connect

    Ono, Kenjiro; Hirohata, Mie; Yamada, Masahito . E-mail: m-yamada@med.kanazawa-u.ac.jp

    2006-03-24

    Inhibition of the formation of {beta}-amyloid fibrils (fA{beta}), as well as the destabilization of preformed fA{beta} in the CNS would be attractive therapeutic targets for the treatment of Alzheimer's disease (AD). Using fluorescence spectroscopic analysis with thioflavin T and electron microscopic studies, we examined the effects of {alpha}-lipoic acid (LA) and the metabolic product of LA, dihydrolipoic acid (DHLA), on the formation, extension, and destabilization of fA{beta} at pH 7.5 at 37 {sup o}C in vitro. LA and DHLA dose-dependently inhibited fA{beta} formation from amyloid {beta}-protein, as well as their extension. Moreover, they destabilized preformed fA{beta}s. LA and DHLA could be key molecules for the development of therapeutics for AD.

  8. Visco-resistive tearing in thin current sheets.

    NASA Astrophysics Data System (ADS)

    Velli, M. M. C.; Tenerani, A.; Rappazzo, A. F.; Pucci, F.

    2014-12-01

    How fast magnetic energy release is triggered and occurs in high Lundquist (S) and high Reynolds number ( R ) plasmas such as that of the solar corona is a fundamental problem for understanding phenomena ranging from coronal heating to flares and CMEs. Diffusion or collisional reconnection driven by macroscopic flows in quasi-steady Sweet-Parker (SP) current sheets are processes far too slow to fit observational data. Spontaneous reconnection, driven by the onset of the tearing instability inside current sheets, provides an alternative paradigm to SP reconnection. Nevertheless, as long as macroscopic current layers are considered, the growth of such an instability is also a slow process. Recently it has been shown that SP current sheets are rapidly unstable in high S plasmas, indeed have a growth rate diverging with increasing S. It has been suggested that such instabilities are triggered during the nonlinear stage of the primary tearing instability of a macroscopic layer. The formation of plasmoids in this presumed SP sheet speeds up the reconnection rate to ideal values. Recently, we have suggested that SP sheets can not be realized in quasi-ideal plasmas, and that the plasmoid instability is triggered on a much larger scale (i.e. with current sheets having a much larger ration of thickness to length than SP). Here we present a linear parametric study of the tearing instability for a Harris current sheet, while taking into account both viscosity and current sheets of variable aspect ratios. The present study shows that an explosive growth of the reconnection rate may be reached during the linear stage, once a critical width of the current layer is reached. In the absence of a strong guide field this depends on viscosity and a range of critical aspect ratios can be found for different values of S, R, or S and Prandtl number.

  9. Rolling Up a Monolayer MoS2 Sheet.

    PubMed

    Meng, Jianling; Wang, Guole; Li, Xiaomin; Lu, Xiaobo; Zhang, Jing; Yu, Hua; Chen, Wei; Du, Luojun; Liao, Mengzhou; Zhao, Jing; Chen, Peng; Zhu, Jianqi; Bai, Xuedong; Shi, Dongxia; Zhang, Guangyu

    2016-07-01

    MoS2 nanoscrolls are formed by argon plasma treatment on monolayer MoS2 sheet. The nanoscale scroll formation is attributed to the partial removal of top sulfur layer in MoS2 during the argon plasma treatment process. This convenient, solvent-free, and high-yielding nanoscroll formation technique is also feasible for other 2D transition metal dichalcogenides.

  10. Cartilage engineering using chondrocyte cell sheets and its application in reconstruction of microtia.

    PubMed

    Zhou, Libin; Ding, Ruiying; Li, Baowei; Han, Haolun; Wang, Hongnan; Wang, Gang; Xu, Bingxin; Zhai, Suoqiang; Wu, Wei

    2015-01-01

    The imperfections of scaffold materials have hindered the clinical application of cartilage tissue engineering. The recently developed cell-sheet technique is adopted to engineer tissues without scaffold materials, thus is considered being potentially able to overcome the problems concerning the scaffold imperfections. This study constructed monolayer and bilayer chondrocyte cell sheets and harvested the sheets with cell scraper instead of temperature-responsive culture dishes. The properties of the cultured chondrocyte cell sheets and the feasibility of cartilage engineering using the chondrocyte cell sheets was further investigated via in vitro and in vivo study. Primary extracellular matrix (ECM) formation and type II collagen expression was detected in the cell sheets during in vitro culture. After implanted into nude mice for 8 weeks, mature cartilage discs were harvested. The morphology of newly formed cartilage was similar in the constructs originated from monolayer and bilayer chondrocyte cell sheet. The chondrocytes were located within evenly distributed ovoid lacunae. Robust ECM formation and intense expression of type II collagen was observed surrounding the evenly distributed chondrocytes in the neocartilages. Biochemical analysis showed that the DNA contents of the neocartilages were higher than native human costal cartilage; while the contents of the main component of ECM, glycosaminoglycan and hydroxyproline, were similar to native human costal cartilage. In conclusion, the chondrocyte cell sheet constructed using the simple and low-cost technique is basically the same with the cell sheet cultured and harvested in temperature-responsive culture dishes, and can be used for cartilage tissue engineering.

  11. Hypoxia Created Human Mesenchymal Stem Cell Sheet for Prevascularized 3D Tissue Construction.

    PubMed

    Zhang, Lijun; Xing, Qi; Qian, Zichen; Tahtinen, Mitchell; Zhang, Zhaoqiang; Shearier, Emily; Qi, Shaohai; Zhao, Feng

    2016-02-01

    3D tissue based on human mesenchymal stem cell (hMSC) sheets offers many interesting opportunities for regenerating multiple types of connective tissues. Prevascularizing hMSC sheets with endothelial cells (ECs) will improve 3D tissue performance by supporting cell survival and accelerating integration with host tissue. It is hypothesized that hypoxia cultured hMSC sheets can promote microvessel network formation and preserve stemness of hMSCs. This study investigates the vascularization of hMSC sheets under different oxygen tensions. It is found that the HN condition, in which hMSC sheets formed under physiological hypoxia (2% O2 ) and then cocultured with ECs under normoxia (20% O2 ), enables longer and more branched microvessel network formation. The observation is corroborated by higher levels of angiogenic factors in coculture medium. Additionally, the hypoxic hMSC sheet is more uniform and less defective, which facilitates fabrication of 3D prevascularized tissue construct by layering the prevascularized hMSC sheets and maturing in rotating wall vessel bioreactor. The hMSCs in the 3D construct still maintain multilineage differentiation ability, which indicates the possible application of the 3D construct for various connective tissues regeneration. These results demonstrate that hypoxia created hMSC sheets benefit the microvessel growth and it is feasible to construct 3D prevascularized tissue construct using the prevascularized hMSC sheets.

  12. Cartilage engineering using chondrocyte cell sheets and its application in reconstruction of microtia.

    PubMed

    Zhou, Libin; Ding, Ruiying; Li, Baowei; Han, Haolun; Wang, Hongnan; Wang, Gang; Xu, Bingxin; Zhai, Suoqiang; Wu, Wei

    2015-01-01

    The imperfections of scaffold materials have hindered the clinical application of cartilage tissue engineering. The recently developed cell-sheet technique is adopted to engineer tissues without scaffold materials, thus is considered being potentially able to overcome the problems concerning the scaffold imperfections. This study constructed monolayer and bilayer chondrocyte cell sheets and harvested the sheets with cell scraper instead of temperature-responsive culture dishes. The properties of the cultured chondrocyte cell sheets and the feasibility of cartilage engineering using the chondrocyte cell sheets was further investigated via in vitro and in vivo study. Primary extracellular matrix (ECM) formation and type II collagen expression was detected in the cell sheets during in vitro culture. After implanted into nude mice for 8 weeks, mature cartilage discs were harvested. The morphology of newly formed cartilage was similar in the constructs originated from monolayer and bilayer chondrocyte cell sheet. The chondrocytes were located within evenly distributed ovoid lacunae. Robust ECM formation and intense expression of type II collagen was observed surrounding the evenly distributed chondrocytes in the neocartilages. Biochemical analysis showed that the DNA contents of the neocartilages were higher than native human costal cartilage; while the contents of the main component of ECM, glycosaminoglycan and hydroxyproline, were similar to native human costal cartilage. In conclusion, the chondrocyte cell sheet constructed using the simple and low-cost technique is basically the same with the cell sheet cultured and harvested in temperature-responsive culture dishes, and can be used for cartilage tissue engineering. PMID:25755694

  13. Ureidopenicillins and beta-lactam/beta-lactamase inhibitor combinations.

    PubMed

    Bush, L M; Johnson, C C

    2000-06-01

    Although research and development of new penicillins have declined, penicillins continue to be essential antibiotics for the treatment and prophylaxis of infectious diseases. The most recent additions are the ureidopenicillins and beta-lactam/beta-lactamase inhibitor combinations. This article reviews the spectrum of activity, toxicity, pharmacokinetics, and clinical uses of the ureidopenicillins, and the beta-lactam/beta-lactamase inhibitor combination agents.

  14. Theoretical modeling of the plasma-assisted catalytic growth and field emission properties of graphene sheet

    SciTech Connect

    Sharma, Suresh C.; Gupta, Neha

    2015-12-15

    A theoretical modeling for the catalyst-assisted growth of graphene sheet in the presence of plasma has been investigated. It is observed that the plasma parameters can strongly affect the growth and field emission properties of graphene sheet. The model developed accounts for the charging rate of the graphene sheet; number density of electrons, ions, and neutral atoms; various elementary processes on the surface of the catalyst nanoparticle; surface diffusion and accretion of ions; and formation of carbon-clusters and large graphene islands. In our investigation, it is found that the thickness of the graphene sheet decreases with the plasma parameters, number density of hydrogen ions and RF power, and consequently, the field emission of electrons from the graphene sheet surface increases. The time evolution of the height of graphene sheet with ion density and sticking coefficient of carbon species has also been examined. Some of our theoretical results are in compliance with the experimental observations.

  15. Acetylcholinesterase, a senile plaque component, affects the fibrillogenesis of amyloid-beta-peptides.

    PubMed

    Alvarez, A; Bronfman, F; Pérez, C A; Vicente, M; Garrido, J; Inestrosa, N C

    1995-12-01

    Acetylcholinesterase (AChE) colocalizes with amyloid-beta peptide (A beta) deposits present in the brain of Alzheimer's patients. Recent studies showed that A beta 1-40 can adopt two different conformational states in solution (an amyloidogenic conformer, A beta ac, and a non-amyloidogenic conformer, A beta nac) which have distinct abilities to form amyloid fibrils. We report here that AChE binds A beta nac and accelerates amyloid formation by the same peptide. No such effect was observed with A beta ac, the amyloidogenic conformer, suggesting that AChE acts as a 'pathological chaperone' inducing a conformational transition from A beta nac into A beta ac in vitro.

  16. Beta experiment flight report

    NASA Technical Reports Server (NTRS)

    1982-01-01

    A focused laser Doppler velocimeter system was developed for the measurement of atmospheric backscatter (beta) from aerosols at infrared wavelengths. The system was flight tested at several different locations and the results of these tests are summarized.

  17. On Jovian plasma sheet structure

    NASA Astrophysics Data System (ADS)

    Khurana, Krishan K.; Kivelson, Margaret G.

    1989-09-01

    Several models of Jovian plasma sheet structure are studied, focusing on the ways in which they organize aspects of the observed Voyager 2 magnetic field characteristics as a function of radial distance from Jupiter. A technique which locates the interfaces between the plasma sheet and the lobes from magnetic data is presented. This boundary location is used to test models of the magnetotail. Improved variations of the hinged-magnetodisk and the magnetic anomaly models are given in which the parameters are optimized by using structural information from observed magnetic equator and plasma-sheet-lobe boundary crossings.

  18. Microcomponent chemical process sheet architecture

    DOEpatents

    Wegeng, R.S.; Drost, M.K.; Call, C.J.; Birmingham, J.G.; McDonald, C.E.; Kurath, D.E.; Friedrich, M.

    1998-09-22

    The invention is a microcomponent sheet architecture wherein macroscale unit processes are performed by microscale components. The sheet architecture may be a single laminate with a plurality of separate microcomponent sections or the sheet architecture may be a plurality of laminates with one or more microcomponent sections on each laminate. Each microcomponent or plurality of like microcomponents perform at least one chemical process unit operation. A first laminate having a plurality of like first microcomponents is combined with at least a second laminate having a plurality of like second microcomponents thereby combining at least two unit operations to achieve a system operation. 26 figs.

  19. Microcomponent chemical process sheet architecture

    DOEpatents

    Wegeng, Robert S.; Drost, M. Kevin; Call, Charles J.; Birmingham, Joseph G.; McDonald, Carolyn Evans; Kurath, Dean E.; Friedrich, Michele

    1998-01-01

    The invention is a microcomponent sheet architecture wherein macroscale unit processes are performed by microscale components. The sheet architecture may be a single laminate with a plurality of separate microcomponent sections or the sheet architecture may be a plurality of laminates with one or more microcomponent sections on each laminate. Each microcomponent or plurality of like microcomponents perform at least one chemical process unit operation. A first laminate having a plurality of like first microcomponents is combined with at least a second laminate having a plurality of like second microcomponents thereby combining at least two unit operations to achieve a system operation.

  20. High beta multipoles

    SciTech Connect

    Prager, S C

    1982-05-01

    Multipoles are being employed as devices to study fusion issues and plasma phenomena at high values of beta (plasma pressure/magnetic pressure) in a controlled manner. Due to their large volume, low magnetic field (low synchrotron radiation) region, they are also under consideration as potential steady state advanced fuel (low neutron yield) reactors. Present experiments are investigating neoclassical (bootstrap and Pfirsch-Schlueter) currents and plasma stability at extremely high beta.

  1. Superfund fact sheet: The removal program. Fact sheet

    SciTech Connect

    Not Available

    1992-09-01

    The fact sheet describes the Superfund Emergency Response Program, a program specifically designed to respond to multi-media hazardous materials accidents (e.g. illegal disposal or improper handling of materials, transportation accidents, chemical fires) that endanger people and/or the environment. Explanations of how the removal program works and how the affected communities are involved are given. The fact sheet is one in a series providing reference information about Superfund issues and is intended for readers with no scientific training.

  2. Scrolling of Suspended CVD Graphene Sheets

    NASA Astrophysics Data System (ADS)

    Martynov, Oleg; Yeom, Sinchul; Bockrath, Marc; UC: Riverside Team

    Carbon Nanoscrolls, one dimensional spiral forms of graphitic carbon, have attracted recent interest due to their novel proposed properties. Although various production methods and studies of carbon nanoscrolls have been performed, low yield and poor controllability of their synthesis have slowed progress in this field. Suspended graphene membranes and carbon nanotubes have been predicted as promising systems for the formation of graphene scrolls. We have suspended chemical vapor deposition (CVD)-grown graphene over large holes in a Si/SiO2 substrate to make suspended membranes upon which nanotubes are placed. Initial experiments have been performed showing that tears or cuts of the suspended sheet can initiate scrolling. Our latest progress towards carbon nanotube initiated formation of graphene scrolls and suspended CVD graphene scrolling, along with measurements of these novel structures will be presented.

  3. Selectively reflective transparent sheets

    NASA Astrophysics Data System (ADS)

    Waché, Rémi; Florescu, Marian; Sweeney, Stephen J.; Clowes, Steven K.

    2015-08-01

    We investigate the possibility to selectively reflect certain wavelengths while maintaining the optical properties on other spectral ranges. This is of particular interest for transparent materials, which for specific applications may require high reflectivity at pre-determined frequencies. Although there exist currently techniques such as coatings to produce selective reflection, this work focuses on new approaches for mass production of polyethylene sheets which incorporate either additives or surface patterning for selective reflection between 8 to 13 μ m. Typical additives used to produce a greenhouse effect in plastics include particles such as clays, silica or hydroxide materials. However, the absorption of thermal radiation is less efficient than the decrease of emissivity as it can be compared with the inclusion of Lambertian materials. Photonic band gap engineering by the periodic structuring of metamaterials is known in nature for producing the vivid bright colors in certain organisms via strong wavelength-selective reflection. Research to artificially engineer such structures has mainly focused on wavelengths in the visible and near infrared. However few studies to date have been carried out to investigate the properties of metastructures in the mid infrared range even though the patterning of microstructure is easier to achieve. We present preliminary results on the diffuse reflectivity using FDTD simulations and analyze the technical feasibility of these approaches.

  4. Preformed {beta}-amyloid fibrils are destabilized by coenzyme Q{sub 10} in vitro

    SciTech Connect

    Ono, Kenjiro; Hasegawa, Kazuhiro; Naiki, Hironobu; Yamada, Masahito . E-mail: m-yamada@med.kanazawa-u.ac.jp

    2005-04-29

    Inhibition of the formation of {beta}-amyloid fibrils (fA{beta}), as well as the destabilization of preformed fA{beta} in the CNS, would be attractive therapeutic targets for the treatment of Alzheimer's disease (AD). We reported previously that nordihydroguaiaretic acid (NDGA) and wine-related polyphenol, myricetin (Myr), inhibit fA{beta} formation from A{beta} and destabilize preformed fA{beta} in vitro. Using fluorescence spectroscopic analysis with thioflavin T and electron microscopic studies, we examined the effects of coenzyme Q{sub 10} (CoQ{sub 10}) on the formation, extension, and destabilization of fA{beta} at pH 7.5 at 37 deg C in vitro. We next compared the anti-amyloidogenic activities of CoQ{sub 10} with NDGA and Myr. CoQ{sub 10} dose-dependently inhibited fA{beta} formation from amyloid {beta}-peptide (A{beta}), as well as their extension. Moreover, it destabilized preformed fA{beta}s. The anti-amyloidogenic effects of CoQ{sub 10} were slightly weaker than those of NDGA and Myr. CoQ{sub 10} could be a key molecule for the development of therapeutics for AD.

  5. Low Temperature Sheet Forming

    NASA Astrophysics Data System (ADS)

    Voges-Schwieger, Kathrin; Hübner, Sven; Behrens, Bernd-Arno

    2011-05-01

    Metastable austenitic stainless steels change their lattice during forming operations by strain-induced alpha'-martensite formation. Temperatures below T = 20° C can accelerate the phase transformation while temperatures above T = 60° C may suppress the formation of martensite during the forming operation. In past investigations, the effect of high-strength martensitic regions in an austenitic ductile lattice was used in crash relevant parts for transportation vehicles. The local martensitic regions act as reinforcements leading to an increase in crash energy absorption. Moreover, they control the folding behavior as well as the force-distance-characteristic and increase the buckling resistance. This paper deals with a concerted thermomechanical drawing process to increase the local formation of alpha'-martensite caused by low temperatures.

  6. Three-dimensional solution structure of beta cryptogein, a beta elicitin secreted by a phytopathogenic fungus Phytophthora cryptogea.

    PubMed Central

    Fefeu, S.; Bouaziz, S.; Huet, J. C.; Pernollet, J. C.; Guittet, E.

    1997-01-01

    Cryptogein belongs to a new family of 10-kDa proteins called elicitins. Elicitins are necrotic and signaling proteins secreted by Phytophthora spp. responsible for the incompatible reaction and systemic hypersensitive-like necroses of diverse plant species leading to resistance against fungal or bacterial plant pathogens. The solution structure of beta cryptogein from Phytophthora cryptogea fungus was determined by using multidimensional heteronuclear nuclear magnetic resonance spectroscopy. A set of 18 structures was calculated using 1360 NOE-derived distance restraints and 40 dihedral angle restraints obtained from 3JHNH alpha couplings. The RMS deviation from the mean structure is 0.87 +/- 0.14 A for backbone atoms and 1.34 +/- 0.14 A for all the non-hydrogen atoms of residues 2 to 98. The structure of beta cryptogein reveals a novel protein fold, with five helices and a double-stranded beta-sheet facing an omega-loop. One edge of the beta-sheet and the adjacent face of the omega-loop form a hydrophobic cavity. This cavity made of highly conserved residues represents a plausible binding site. Residue 13, which has been identified from directed mutagenesis and natural sequence comparison studies as a key amino acid involved in the differential control of necrosis, is surface exposed and could contribute to the binding to a ligand or a receptor. The solution structure is close to the X-ray structure, with slight differences lightly due to the crystal packing. PMID:9385630

  7. Sports Injury Prevention Tip Sheet

    MedlinePlus

    ... Finance Human Resources and Administrative Services Information Technology Marketing and Sales Membership Practice Public Affairs Quality Publishing ... Feedback Recent a a a print email share Facebook Twitter 2016 Sports Injury Prevention Tip Sheet 3/ ...

  8. Concentrating Solar Power (Fact Sheet)

    SciTech Connect

    Not Available

    2010-08-01

    Fact sheet describing the overall capabilities of the NREL CSP Program: collector/receiver characterization, advanced reflector and absorber materials, thermal storage and advanced heat transfer fluids, and CSP modeling and analysis.

  9. Analysis of a Sheet Silicate.

    ERIC Educational Resources Information Center

    Adams, J. M.; Evans, S.

    1980-01-01

    Describes a student project in analytical chemistry using sheet silicates. Provides specific information regarding the use of phlogopite in an experiment to analyze samples for silicon, aluminum, magnesium, iron, potassium, and fluoride. (CS)

  10. Measurements and Characterization (Fact Sheet)

    SciTech Connect

    Not Available

    2011-06-01

    Capabilities fact sheet for the National Center for Photovoltaics: Measurements and Characterization that includes scope, core competencies and capabilities, and contact/web information for Analytical Microscopy, Electro-Optical Characterization, Surface Analysis, and Cell and Module Performance.

  11. SEER Cancer Stat Fact Sheets

    Cancer.gov

    Cancer Statistical Fact Sheets are summaries of common cancer types developed to provide an overview of frequently-requested cancer statistics including incidence, mortality, survival, stage, prevalence, and lifetime risk.

  12. Beta-cardiotoxin: a new three-finger toxin from Ophiophagus hannah (king cobra) venom with beta-blocker activity.

    PubMed

    Rajagopalan, Nandhakishore; Pung, Yuh Fen; Zhu, Yi Zhun; Wong, Peter Tsun Hon; Kumar, Prakash P; Kini, R Manjunatha

    2007-11-01

    Snake venoms have provided a number of novel ligands with therapeutic potential. We have constructed a partial cDNA library from the mRNA of Ophiophagus hannah (king cobra) venom gland tissue and identified five new genes encoding proteins belonging to the three-finger toxin family of snake venom proteins. We have isolated and characterized one of these beta-sheet containing proteins with a mass of 7012.43 +/- 0.91 Da from the venom. The protein was nonlethal up to a dose of 10 mg/kg when injected intraperitoneally into Swiss albino mice. However, it induces labored breathing and death at a dose of 100 mg/kg. It does not show any hemolytic or anticoagulant activity. It caused a dose-dependent decrease of heart rate in vivo (anesthetized Sprague-Dawley rats) and also ex vivo (Langendorff isolated rat heart). This is in contrast to classical cardiotoxins from snake venom that increase the heart rate in animals. Radioligand displacement studies showed that this protein targets beta-adrenergic receptors with a binding affinity (Ki) of 5.3 and 2.3 microM toward beta1 and beta2 subtypes, respectively, to bring about its effect, and hence, it was named as beta-cardiotoxin. This is the first report of a natural exogenous beta-blocker. PMID:17616557

  13. Beta-cardiotoxin: a new three-finger toxin from Ophiophagus hannah (king cobra) venom with beta-blocker activity.

    PubMed

    Rajagopalan, Nandhakishore; Pung, Yuh Fen; Zhu, Yi Zhun; Wong, Peter Tsun Hon; Kumar, Prakash P; Kini, R Manjunatha

    2007-11-01

    Snake venoms have provided a number of novel ligands with therapeutic potential. We have constructed a partial cDNA library from the mRNA of Ophiophagus hannah (king cobra) venom gland tissue and identified five new genes encoding proteins belonging to the three-finger toxin family of snake venom proteins. We have isolated and characterized one of these beta-sheet containing proteins with a mass of 7012.43 +/- 0.91 Da from the venom. The protein was nonlethal up to a dose of 10 mg/kg when injected intraperitoneally into Swiss albino mice. However, it induces labored breathing and death at a dose of 100 mg/kg. It does not show any hemolytic or anticoagulant activity. It caused a dose-dependent decrease of heart rate in vivo (anesthetized Sprague-Dawley rats) and also ex vivo (Langendorff isolated rat heart). This is in contrast to classical cardiotoxins from snake venom that increase the heart rate in animals. Radioligand displacement studies showed that this protein targets beta-adrenergic receptors with a binding affinity (Ki) of 5.3 and 2.3 microM toward beta1 and beta2 subtypes, respectively, to bring about its effect, and hence, it was named as beta-cardiotoxin. This is the first report of a natural exogenous beta-blocker.

  14. Energy information sheets, September 1996

    SciTech Connect

    1996-09-01

    The National Energy Information Center (NEIC), as part of its mission, provides energy information and referral assistance to Federal, State, and local governments, the academic community, business and industrial organizations, and the public. The Energy Information Sheets was developed to provide general information on various aspects of fuel production, prices, consumption, and capability. Additional information on related subject matter can be found in other Energy Information Administration (EIA) publications as referenced at the end of each sheet.

  15. Energy information sheets, July 1998

    SciTech Connect

    1998-07-01

    The National Energy Information Center (NEIC), as part of its mission, provides energy information and referral assistance to Federal, State, and local governments, the academic community, business and industrial organizations, and the public. The Energy Information Sheets was developed to provide general information on various aspects of fuel production, prices, consumption, and capability. Additional information on related subject matter can be found in other Energy Information Administration (EIA) publications as referenced at the end of each sheet.

  16. Absence of amyloid-beta in lenses of Alzheimer patients: a confocal Raman microspectroscopic study.

    PubMed

    Michael, Ralph; Otto, Cees; Lenferink, Aufried; Gelpi, Ellen; Montenegro, Gustavo A; Rosandić, Jurja; Tresserra, Francisco; Barraquer, Rafael I; Vrensen, Gijs F J M

    2014-02-01

    We have compared the protein profiles in plaques and tangles in the hippocampus of post-mortem Alzheimer brains and in opaque and clear regions in the deep cortex of eye lenses of the same donors. From the 7 Alzheimer donors studied, 1 had pronounced bilateral cortical lens opacities, 1 moderate and 5 only minor or no cortical opacities. We focused on beta-sheet levels, a hallmarking property of amyloid-beta, the major protein of plaques and tau protein, the major protein of tangles in Alzheimer brains. Confocal Raman microspectroscopy and imaging was used in combination with hierarchical cluster analysis. Plaques and tangles show high levels of beta-sheets with a beta-sheet to protein ratio of 1.67. This ratio is 1.12 in unaffected brain tissue surrounding the plaques and tangles. In the lenses this ratio is 1.17 independently of the presence or absence of opacities. This major difference in beta-sheet conformation between hippocampus and lens is supported by Congo red and immunostaining of amyloid-beta and tau which were positive for plaques and tangles in the hippocampus but fully negative for the lens irrespective of the presence or absence of opacities. In line with a previous study (Michael et al., 2013) we conclude that cortical lens opacities are not typical for Alzheimer patients and are not hallmarked by accumulation of amyloid-beta, and can thus not be considered as predictors or indicators of Alzheimer disease as claimed by Goldstein et al. (2003).

  17. The current-voltage relationship in auroral current sheets

    NASA Technical Reports Server (NTRS)

    Weimer, D. R.; Gurnett, D. A.; Goertz, C. K.; Menietti, J. D.; Burch, J. L.

    1987-01-01

    The current-voltage relation within narrow auroral current sheets is examined through the use of high-resolution data from the high altitude Dynamics Explorer 1 satellite. The north-south perpendicular electric field and the east-west magnetic field are shown for three cases in which there are large amplitude, oppositely directed paired electric fields and narrow current sheets. These data are shown to indicate that there is a linear Ohm's law relationship between the current density and the parallel potential drop within the narrow current sheets. This linear relationship had previously been verified for large-scale auroral formations greater than 20 km wide at the ionosphere. The evidence shown here extends our knowledge down to the scale size of discrete auroral arcs.

  18. Dynamic of Current Sheets and Their Associated Particle Energization

    SciTech Connect

    Li, Hui; Guo, Fan; Makwan, Kirit; Li, Xiaocan; Zhandrin, Vladimir; Daughton, William Scott

    2015-08-19

    Magnetic reconnection in current sheets has relevance to Earth's magnetosphere, solar flares, high-energy astrophysics (pulsar wind nebula (e.g. Crab Nebula), gamma-ray bursts, black hole jets), and laboratory plasma/fusion. Data are shown for several cases with varying values of configuration energy Ec and β. Several conclusions were drawn: Depending on the “configuration energy”, the formation, shape, and lifetime of current sheets can vary. Plasma condition (configuration, β, driving, etc.) strongly affect the efficiency of particle acceleration. For low β and general “configuration energy”, particle heating is expected. For low β, large and long-lived current sheets, it is possible to produce highly non-thermal particles via collisionless plasmoid reconnection.

  19. In silico and in vitro studies to elucidate the role of Cu2+ and galanthamine as the limiting step in the amyloid beta (1-42) fibrillation process.

    PubMed

    Hernández-Rodríguez, Maricarmen; Correa-Basurto, José; Benitez-Cardoza, Claudia G; Resendiz-Albor, Aldo Arturo; Rosales-Hernández, Martha C

    2013-10-01

    The formation of fibrils and oligomers of amyloid beta (Aβ) with 42 amino acid residues (Aβ 1-42 ) is the most important pathophysiological event associated with Alzheimer's disease (AD). The formation of Aβ fibrils and oligomers requires a conformational change from an α-helix to a β-sheet conformation, which is encouraged by the formation of a salt bridge between Asp 23 or Glu 22 and Lys 28. Recently, Cu(2+) and various drugs used for AD treatment, such as galanthamine (Reminyl(®) ), have been reported to inhibit the formation of Aβ fibrils. However, the mechanism of this inhibition remains unclear. Therefore, the aim of this work was to explore how Cu(2+) and galanthamine prevent the formation of Aβ1-42 fibrils using molecular dynamics (MD) simulations (20 ns) and in vitro studies using fluorescence and circular dichroism (CD) spectroscopies. The MD simulations revealed that Aβ1-42 acquires a characteristic U-shape before the α-helix to β-sheet conformational change. The formation of a salt bridge between Asp 23 and Lys 28 was also observed beginning at 5 ns. However, the MD simulations of Aβ 1-42 in the presence of Cu(2+) or galanthamine demonstrated that both ligands prevent the formation of the salt bridge by either binding to Glu 22 and Asp 23 (Cu(2+) ) or to Lys 28 (galanthamine), which prevents Aβ 1-42 from adopting the U-characteristic conformation that allows the amino acids to transition to a β-sheet conformation. The docking results revealed that the conformation obtained by the MD simulation of a monomer from the 1Z0Q structure can form similar interactions to those obtained from the 2BGE structure in the oligomers. The in vitro studies demonstrated that Aβ remains in an unfolded conformation when Cu(2+) and galanthamine are used. Then, ligands that bind Asp 23 or Glu 22 and Lys 28 could therefore be used to prevent β turn formation and, consequently, the formation of Aβ fibrils.

  20. In silico and in vitro studies to elucidate the role of Cu2+ and galanthamine as the limiting step in the amyloid beta (1–42) fibrillation process

    PubMed Central

    Hernández-Rodríguez, Maricarmen; Correa-Basurto, José; Benitez-Cardoza, Claudia G; Resendiz-Albor, Aldo Arturo; Rosales-Hernández, Martha C

    2013-01-01

    The formation of fibrils and oligomers of amyloid beta (Aβ) with 42 amino acid residues (Aβ1–42) is the most important pathophysiological event associated with Alzheimer's disease (AD). The formation of Aβ fibrils and oligomers requires a conformational change from an α-helix to a β-sheet conformation, which is encouraged by the formation of a salt bridge between Asp 23 or Glu 22 and Lys 28. Recently, Cu2+ and various drugs used for AD treatment, such as galanthamine (Reminyl®), have been reported to inhibit the formation of Aβ fibrils. However, the mechanism of this inhibition remains unclear. Therefore, the aim of this work was to explore how Cu2+ and galanthamine prevent the formation of Aβ1–42 fibrils using molecular dynamics (MD) simulations (20 ns) and in vitro studies using fluorescence and circular dichroism (CD) spectroscopies. The MD simulations revealed that Aβ1–42 acquires a characteristic U-shape before the α-helix to β-sheet conformational change. The formation of a salt bridge between Asp 23 and Lys 28 was also observed beginning at 5 ns. However, the MD simulations of Aβ1−42 in the presence of Cu2+ or galanthamine demonstrated that both ligands prevent the formation of the salt bridge by either binding to Glu 22 and Asp 23 (Cu2+) or to Lys 28 (galanthamine), which prevents Aβ1−42 from adopting the U-characteristic conformation that allows the amino acids to transition to a β-sheet conformation. The docking results revealed that the conformation obtained by the MD simulation of a monomer from the 1Z0Q structure can form similar interactions to those obtained from the 2BGE structure in the oligomers. The in vitro studies demonstrated that Aβ remains in an unfolded conformation when Cu2+ and galanthamine are used. Then, ligands that bind Asp 23 or Glu 22 and Lys 28 could therefore be used to prevent β turn formation and, consequently, the formation of Aβ fibrils. PMID:23904252

  1. Global ice-sheet system interlocked by sea level

    SciTech Connect

    Denton, G.H.; Hughes, T.J.; Karlen, W.

    1986-01-01

    Denton and Hughes postulated that sea level linked a global ice-sheet system with both terrestrial and grounded marine components during later Quaternary ice ages. Summer temperature changes near Northern Hemisphere melting margins initiated sea-level fluctuations that controlled marine components in both polar hemispheres. It was further proposed that variations of this ice-sheet system amplified and transmitted Milankovitch summer half-year insolation changes between 45 and 75/sup 0/N into global climatic changes. New tests of this hypothesis implicate sea level as a major control of the areal extent of grounded portions of the Antarctic Ice Sheet. But factors other than areal changes of the grounded Antarctic Ice Sheet may have strongly influenced Southern Hemisphere climate and terminated the last ice age simultaneously in both polar hemispheres. Atmospheric carbon dioxide linked to high-latitude oceans is the most likely candidate, but another potential influence was high-frequency climatic oscillations. It is postulated that variations in atmospheric carbon dioxide acted through an Antarctic ice shelf linked to the grounded ice sheet to produce and terminate Southern Hemisphere ice-age climate. It is further postulated that Milankovitch summer insolation combined with a warm-high frequency oscillation caused marked recession of Northern Hemisphere ice-sheet melting margins and the North Atlantic polar front about 14,000 /sup 14/C yr B.P. This permitted renewed formation of North Atlantic Deep Water, which could well have controlled atmospheric carbon dioxide. Combined melting and consequent sea-level rise from the three warming factors initiated irreversible collapse of the interlocked global ice-sheet system, which was at its largest but most vulnerable configuration.

  2. Horizontal electromagnetic casting of thin metal sheets

    DOEpatents

    Hull, John R.; Lari, Robert J.; Praeg, Walter F.; Turner, Larry R.

    1987-01-01

    Thin metal sheets are cast by magnetically suspending molten metal deposited within a ferromagnetic yoke and between AC conducting coils and linearly displacing the magnetically levitated liquid metal while it is being cooled to form a solid metal sheet. Magnetic flux increases as the molten metal sheet moves downward and decreases as the molten metal sheet moves upward to stabilize the sheet and maintain it in equilibrium as it is linearly displaced and solidified by cooling gases. A conducting shield is electrically coupled to the molten metal sheet by means of either metal sheet engaging rollers or brushes on the solidified metal, and by means of an electrode in the vessel containing the molten metal thereby providing a return path for the eddy currents induced in the metal sheet by the AC coil generated magnetic flux. Variation in the geometry of the conducting shield allows the magnetic flux between the metal sheet and the conducting shield to be varied and the thickness in surface quality of the metal sheet to be controlled. Side guards provide lateral containment for the molten metal sheet and stabilize and shape the magnetic field while a leader sheet having electromagnetic characteristics similar to those of the metal sheet is used to start the casting process and precedes the molten metal sheet through the magnet and forms a continuous sheet therewith. The magnet may be either U-shaped with a single racetrack coil or may be rectangular with a pair of facing bedstead coils.

  3. Horizontal electromagnetic casting of thin metal sheets

    DOEpatents

    Hull, John R.; Lari, Robert J.; Praeg, Walter F.; Turner, Larry R.

    1988-01-01

    Thin metal sheets are cast by magnetically suspending molten metal deposited within a ferromagnetic yoke and between AC conducting coils and linearly displacing the magnetically levitated liquid metal while it is being cooled to form a solid metal sheet. Magnetic flux increases as the molten metal sheet moves downward and decreases as the molten metal sheet moves upward to stabilize the sheet and maintain it in equilibrium as it is linearly displaced and solidified by cooling gases. A conducting shield is electrically coupled to the molten metal sheet by means of either metal sheet engaging rollers or brushes on the solidified metal, and by means of an electrode in the vessel containing the molten metal thereby providing a return path for the eddy currents induced in the metal sheet by the AC coil generated magnetic flux. Variation in the geometry of the conducting shield allows the magnetic flux between the metal sheet and the conducting shield to be varied and the thickness in surface quality of the metal sheet to be controlled. Side guards provide lateral containment for the molten metal sheet and stabilize and shape the magnetic field while a leader sheet having electromagnetic characteristics similar to those of the metal sheet is used to start the casting process and precedes the molten metal sheet through the magnet and forms a continuous sheet therewith. The magnet may be either U-shaped with a single racetrack coil or may be rectangular with a pair of facing bedstead coils.

  4. Synthesis and thermal stability of polycrystalline new divalent [beta][double prime]- and [beta]-ferrites prepared by ion exchange

    SciTech Connect

    Kalogirou, O. Aristotle Univ., Thessaloniki )

    1993-02-01

    Using ion-exchange chemistry the divalent cations Ba[sup 2+], Sr[sup 2+], Ca[sup 2+], Mg[sup 2+], Cd[sup 2+], Pb[sup 2+], Co[sup 2+], Zn[sup 2+], Mn[sup 2+], Fe[sup 2+], and Sn[sup 2+] have been substituted for K[sup +] in polycrystalline CdO-stabilized K-[beta][double prime]-ferrite samples. Ba, Sr, Ca, Mg, Pb, and Cd ion exchange led to the synthesis of new materials, the divalent M[sup 2+]-[beta][double prime]-ferrites (M = Ba, Sr, Ca, Mg) and M[sup 2+]-[beta]-ferrites (M = Cd, Pb), respectively. Co[sup 2+]-diffusion resulted in the formation of a spinel-type Co-ferrite. In the case of Zn, Mn, Fe, and Sn the samples decomposed to [alpha]-Fe[sub 2]O[sub 3]. The thermal stability of the new divalent [beta][double prime]- and [beta]-ferrites was studied either by high-temperature exchange reactions or by air annealing of the exchanged products. Ba- and Sr-[beta][double prime]-ferrites and Pb-[beta]-ferrite converted to M-type hexagonal ferrites with the magnetoplumbite structure, Mg-[beta][double prime]-ferrite decomposed to a spinel-type Mg-ferrite, and Ca-[beta][double prime]-ferrite and Cd-[beta]-ferrite decomposed to [alpha]-Fe[sub 2]O[sub 3]. Composition, lattice parameters, SEM photographs, and magnetic properties of the ferrites formed are given. The magnetic susceptibilities of the divalent [beta][double prime]- or [beta]-ferrites have values between 0.63 and 1.14 [times] 10[sup [minus]4] emu/g[center dot]Oe at room temperature. 41 refs., 1 fig., 4 tabs.

  5. Platelet-derived growth factor (BB homodimer), transforming growth factor-beta 1, and basic fibroblast growth factor in dermal wound healing. Neovessel and matrix formation and cessation of repair.

    PubMed Central

    Pierce, G. F.; Tarpley, J. E.; Yanagihara, D.; Mustoe, T. A.; Fox, G. M.; Thomason, A.

    1992-01-01

    Recombinant platelet-derived growth factor (BB homodimer, rPDGF-BB), transforming growth factor beta 1 (rTGF-beta 1), and basic fibroblast growth factor (rbFGF) can accelerate healing of soft tissues. However, little information is available characterizing the components of wound matrix induced by these growth factors and the molecular mechanisms underlying accelerated repair and wound maturation. In this study, the composition, quantity, and rate of extracellular matrix deposition within growth factor-treated lapine ear excisional wounds were analyzed at different stages of healing using specific histochemical and immunohistochemical stains, coupled with image analysis techniques. Single application of optimal concentrations of each growth factor accelerated normal healing by 30% (P less than 0.0003); rPDGF-BB markedly augmented early glycosaminoglycan (GAG) and fibronectin deposition, but induced significantly greater levels of collagen later in the repair process, compared with untreated wounds rTGF-beta 1 treatment led to rapidly enhanced collagen synthesis and maturation, without increased GAG deposition. In contrast, rbFGF treatment induced a predominantly angiogenic response in wounds, with a marked increase in endothelia and neovessels (P less than 0.0001), and increased wound collagenolytic activity (P less than 0.03). rbFGF-treated wounds did not evolve into collagen-containing scars and continued to accumulate only provisional matrix well past wound closure. These results provide new evidence that growth factors influence wound repair via different mechanisms: 1) rPDGF-BB accelerates deposition of provisional wound matrix; 2) rTGF-beta 1 accelerates deposition and maturation of collagen; and 3) rbFGF induces a profound monocellular angiogenic response which may lead to a marked delay in wound maturation, and the possible loss of the normal signal(s) required to stop repair. These results suggest that specific growth factors may selectively regulate

  6. Immobilization of TiO2 nanofibers on reduced graphene sheets: Novel strategy in electrospinning.

    PubMed

    Pant, Hem Raj; Adhikari, Surya Prasad; Pant, Bishweshwar; Joshi, Mahesh K; Kim, Han Joo; Park, Chan Hee; Kim, Cheol Sang

    2015-11-01

    A simple and efficient approach is developed to immobilize TiO2 nanofibers onto reduced graphene oxide (RGO) sheets. Here, TiO2 nanofiber-intercalated RGO sheets are readily produced by two-step procedure involving the use of electrospinning process to fabricate TiO2 precursor containing polymeric fibers on the surface of GO sheets, followed by simultaneous TiO2 nanofibers formation and GO reduction by calcinations. GO sheets deposited on the collector during electrospinning/electrospray can act as substrate on to which TiO2 precursor containing polymer nanofibers can be deposited which give TiO2 NFs doped RGO sheets on calcinations. Formation of corrugated structure cavities of graphene sheets decorated with TiO2 nanofibers on their surface demonstrates that our method constitutes an alternative top-down strategy toward fabricating verities of nanofiber-decorated graphene sheets. It was found that the synthesized TiO2/RGO composite revealed a remarkable increased in photocatalytic activity compared to pristine TiO2 nanofibers. Therefore, engineering of TiO2 nanofiber-intercalated RGO sheets using proposed facile technique can be considered a promising method for catalytic and other applications.

  7. Polycrystalline Silicon Sheets for Solar Cells by the Improved Spinning Method

    NASA Technical Reports Server (NTRS)

    Maeda, Y.; Yokoyama, T.; Hide, I.

    1984-01-01

    Cost reduction of silicon materials in the photovoltaic program of materials was examined. The current process of producing silicon sheets is based entirely on the conventional Czochralski ingot growth and wafering used in the semiconductor industry. The current technology cannot meet the cost reduction demands for producing low cost silicon sheets. Alternative sheet production processes such as unconventional crystallization are needed. The production of polycrystalline silicon sheets by unconventional ingot technology is the casting technique. Though large grain sheets were obtained by this technique, silicon ribbon growth overcomes deficiencies of the casting process by obtaining the sheet directly from the melt. The need to solve difficulties of growth stability and impurity effects are examined. The direct formation process of polycrystalline silicon sheets with large grain size, smooth surface, and sharp edges from the melt with a high growth rate which will yield low cost silicon sheets for solar cells and the photovoltaic characteristics associated with this type of sheet to include an EBIC study of the grain boundaries are described.

  8. Nuclear Data Sheets for A = 229

    SciTech Connect

    Browne, E.; Tuli, J.K.

    2008-11-15

    The evaluators present in this publication spectroscopic data and level schemes from radioactive decay and nuclear reaction studies for all nuclei with mass number A = 229. These nuclei belong to a region of coexisting quadrupole with possible octupole deformations. The latter have been observed in {sup 229}Ra, but in {sup 229}Pa the experimental evidence is inconclusive. The present evaluation of A = 229, which includes all data received by June 2008, supersedes the 1989 evaluation by Y.A. Akovali, published in Nuclear Data Sheets58, 555 (1989). Highlights of this publication are given below: A comprehensive spectroscopic study of {sup 229}Fr(50.2 s) {beta}- decay using mass-separated sources have provided the first evidence of parity doublets in {sup 229}Ra due to nuclear octupole deformation (1999Fr33). In {sup 229}Th a level at 7.6 5 eV - the closest level to the ground state ever known - has been confirmed through extremely precise measurements of {gamma}-ray energies from {sup 233}U {alpha} decay (1994He08, 2007Be16). A nuclear level at such low energy may be used for studying a large variety of atomic properties associated to nuclear decay. The level structure in {sup 229}Pa has been interpreted in terms of the rotational model (1994Le22). Some authors, however, have proposed the existence of parity doublets as evidence of octupole nuclear deformation (1982Ah08). This interpretation has not been confirmed.

  9. Nuclear Data Sheets for A = 178

    SciTech Connect

    Achterberg, E.; Capurro, O.A.; Marti, G.V.

    2009-07-15

    The present revision of the nuclear structure properties for the nuclides belonging to the A = 178 mass chain contains many improvements and additions to the material presented in the previous evaluation (1994Br18, Nucl. Data Sheets 72, 221 (1994)). Besides updating many values, and including supplementary data for already known levels, transitions and level schemes, the most noteworthy modifications with respect to the prior evaluation are extensive additions to the level schemes of {sup 178}Yb, {sup 178}Hf, {sup 178}Ta, {sup 178}W. {sup 178}Ir, {sup 178}Pt and {sup 178}Hg, based on HI reaction works performed after the last cutoff date (July 1993), and to {sup 178}Hf due to new data from recent Coulomb excitation experiments. Light ion ({sup 3}He, {alpha}) beam experiments have added many data for {sup 178}Ta. Beta decay studies have also provided significant data for {sup 178}W and {sup 178}Pt. Lastly the first report of the identification of {sup 178}Tl and {sup 178}Pb is included.

  10. Study on inclusion interaction of piroxicam with beta-cyclodextrin derivatives.

    PubMed

    Xiliang, Guo; Yu, Yang; Guoyan, Zhao; Guomei, Zhang; Jianbin, Chao; Shaomin, Shuang

    2003-12-01

    The inclusion behavior of piroxicam (PX) with beta-cyclodextrin (beta-CD), hydroxypropyl-beta-cyclodextrin (HP-beta-CD), and carboxymethyl-beta-cyclodextrin (CM-beta-CD) was investigated by using steady-state fluorescence and nuclear magnetic resonance (NMR) technique. The various factors affecting the inclusion process were examined in detail. The remarkable fluorescence emission enhancement upon addition of CDs suggested that cyclodextrins (CDs) were most suitable for inclusion of the uncharged species of PX. The stoichiometry of the PX-CDs inclusion complexes was 1:1, except for beta-CD where a 1:2 inclusion complex was formed. The formation constants showed the strongest inclusion capacity of beta-CD. NMR showed the inclusion mode of PX with CDs.

  11. Transforming growth factor-beta activation in irradiated murine mammary gland.

    PubMed Central

    Barcellos-Hoff, M H; Derynck, R; Tsang, M L; Weatherbee, J A

    1994-01-01

    The biological activity of TGF-beta, an important modulator of cell proliferation and extracellular matrix formation, is governed by dissociation of mature TGF-beta from an inactive, latent TGF-beta complex in a process that is critical to its role in vivo. So far, it has not been possible to monitor activation in vivo since conventional immunohistochemical detection does not accurately discriminate latent versus active TGF-beta, nor have events associated with activation been defined well enough to serve as in situ markers of this process. We describe here a modified immunodetection method using differential antibody staining that allows the specific detection of active versus latent TGF-beta. Under these conditions, we report that an antibody raised to latency-associated peptide detects latent TGF-beta, and we demonstrate that LC(1-30) antibodies specifically recognize active TGF-beta 1 in tumor xenografts overproducing active TGF-beta 1, without cross-reactivity in tumors expressing similar levels of latent TGF-beta 1. We previously reported that TGF-beta immunoreactivity increases in murine mammary gland after whole-body 60Co-gamma radiation exposure. Using differential antibody staining we now show that radiation exposure specifically generates active TGF-beta 1. While latent TGF-beta 1 was widely distributed in unirradiated tissue, active TGF-beta 1 distribution was restricted. Active TGF-beta 1 increased significantly within 1 h of irradiation concomitant with decreased latent TGF-beta immunoreactivity. This rapid shift in immunoreactivity provides the first evidence for activation of TGF-beta in situ. This reciprocal pattern of expression persisted for 3 d and was accompanied by decreased recovery of latent TGF-beta 1 from irradiated tissue. Radiation-induced activation of TGF-beta may have profound implications for understanding tissue effects caused by radiation therapy. Images PMID:8113421

  12. Optimal swimming of a sheet.

    PubMed

    Montenegro-Johnson, Thomas D; Lauga, Eric

    2014-06-01

    Propulsion at microscopic scales is often achieved through propagating traveling waves along hairlike organelles called flagella. Taylor's two-dimensional swimming sheet model is frequently used to provide insight into problems of flagellar propulsion. We derive numerically the large-amplitude wave form of the two-dimensional swimming sheet that yields optimum hydrodynamic efficiency: the ratio of the squared swimming speed to the rate-of-working of the sheet against the fluid. Using the boundary element method, we show that the optimal wave form is a front-back symmetric regularized cusp that is 25% more efficient than the optimal sine wave. This optimal two-dimensional shape is smooth, qualitatively different from the kinked form of Lighthill's optimal three-dimensional flagellum, not predicted by small-amplitude theory, and different from the smooth circular-arc-like shape of active elastic filaments. PMID:25019709

  13. Root-growth-inhibiting sheet

    DOEpatents

    Burton, Frederick G.; Cataldo, Dominic A.; Cline, John F.; Skiens, W. Eugene; Van Voris, Peter

    1993-01-01

    In accordance with this invention, a porous sheet material is provided at intervals with bodies of a polymer which contain a 2,6-dinitroaniline. The sheet material is made porous to permit free passage of water. It may be either a perforated sheet or a woven or non-woven textile material. A particularly desirable embodiment is a non-woven fabric of non-biodegradable material. This type of material is known as a "geotextile" and is used for weed control, prevention of erosion on slopes, and other landscaping purposes. In order to obtain a root repelling property, a dinitroaniline is blended with a polymer which is attached to the geotextile or other porous material.

  14. Root-growth-inhibiting sheet

    DOEpatents

    Burton, F.G.; Cataldo, D.A.; Cline, J.F.; Skiens, W.E.; Van Voris, P.

    1993-01-26

    In accordance with this invention, a porous sheet material is provided at intervals with bodies of a polymer which contain a 2,6-dinitroaniline. The sheet material is made porous to permit free passage of water. It may be either a perforated sheet or a woven or non-woven textile material. A particularly desirable embodiment is a non-woven fabric of non-biodegradable material. This type of material is known as a geotextile'' and is used for weed control, prevention of erosion on slopes, and other landscaping purposes. In order to obtain a root repelling property, a dinitroaniline is blended with a polymer which is attached to the geotextile or other porous material.

  15. Optimal swimming of a sheet

    NASA Astrophysics Data System (ADS)

    Montenegro-Johnson, Thomas D.; Lauga, Eric

    2014-06-01

    Propulsion at microscopic scales is often achieved through propagating traveling waves along hairlike organelles called flagella. Taylor's two-dimensional swimming sheet model is frequently used to provide insight into problems of flagellar propulsion. We derive numerically the large-amplitude wave form of the two-dimensional swimming sheet that yields optimum hydrodynamic efficiency: the ratio of the squared swimming speed to the rate-of-working of the sheet against the fluid. Using the boundary element method, we show that the optimal wave form is a front-back symmetric regularized cusp that is 25% more efficient than the optimal sine wave. This optimal two-dimensional shape is smooth, qualitatively different from the kinked form of Lighthill's optimal three-dimensional flagellum, not predicted by small-amplitude theory, and different from the smooth circular-arc-like shape of active elastic filaments.

  16. beta-Chloronaphthalene

    Integrated Risk Information System (IRIS)

    beta - Chloronaphthalene ; CASRN 91 - 58 - 7 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcin

  17. beta-Propiolactone

    Integrated Risk Information System (IRIS)

    beta - Propiolactone ; CASRN 57 - 57 - 8 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogen

  18. Trichoderma .beta.-glucosidase

    DOEpatents

    Dunn-Coleman, Nigel; Goedegebuur, Frits; Ward, Michael; Yao, Jian

    2006-01-03

    The present invention provides a novel .beta.-glucosidase nucleic acid sequence, designated bgl3, and the corresponding BGL3 amino acid sequence. The invention also provides expression vectors and host cells comprising a nucleic acid sequence encoding BGL3, recombinant BGL3 proteins and methods for producing the same.

  19. The effect of tachykinin neuropeptides on amyloid {beta} aggregation

    SciTech Connect

    Flashner, Efrat; Raviv, Uri; Friedler, Assaf

    2011-04-01

    Research highlights: {yields} Mechanistic explanation of how tachykinin neuropeptides reduce A{beta}-induced neurotoxicity. {yields} Biophysical studies suggest that tachykinins do not modulate the distribution of A{beta} oligomeric states, but rather may incorporate into the fibrils. {yields} A possible strategy to inhibit toxicity of amyloid fibrils. -- Abstract: A hallmark of Alzheimer's disease is production of amyloid {beta} peptides resulting from aberrant cleavage of the amyloid precursor protein. Amyloid {beta} assembles into fibrils under physiological conditions, through formation of neurotoxic intermediate oligomers. Tachykinin peptides are known to affect amyloid {beta} neurotoxicity in cells. To understand the mechanism of this effect, we studied how tachykinins affect A{beta}(1-40) aggregation in vitro. Fibrils grown in the presence of tachykinins exhibited reduced thioflavin T (ThT) fluorescence, while their morphology, observed in transmission electron microscopy (TEM), did not alter. Cross linking studies revealed that the distribution of low molecular weight species was not affected by tachykinins. Our results suggest that there may be a specific interaction between tachykinins and A{beta}(1-40) that allows them to co-assemble. This effect may explain the reduction of A{beta}(1-40) neurotoxicity in cells treated with tachykinins.

  20. An unusual beta-spectrin associated with clustered acetylcholine receptors

    PubMed Central

    1989-01-01

    The clustering of acetylcholine receptors (AChR) in the postsynaptic membrane is an early event in the formation of the neuromuscular junction. The mechanism of clustering is still unknown, but is generally believed to be mediated by the postsynaptic cytoskeleton. We have identified an unusual isoform of beta-spectrin which colocalizes with AChR in AChR clusters isolated from rat myotubes in vitro. A related antigen is present postsynaptically at the neuromuscular junction of the rat. Immunoprecipitation, peptide mapping and immunofluorescence show that the beta-spectrin in AChR clusters resembles but is distinct from the beta-spectrin of human erythrocytes. alpha-Spectrin appears to be absent from AChR clusters. Semiquantitative immunofluorescence techniques indicate that there are from two to seven beta-spectrin molecules present for every clustered AChR, the higher values being obtained from rapidly prepared clusters, the lower values from clusters that require several minutes or more for isolation. Upon incubation of isolated AChR clusters for 1 h at room temperature, beta-spectrin is slowly depleted and the AChR redistribute into microaggregates. The beta-spectrin that remains associated with the myotube membrane is concentrated at these microaggregates. beta- Spectrin is quantitatively lost from clusters upon digestion with chymotrypsin, which causes AChR to redistribute in the plane of the membrane. These results suggest that AChR in clusters is closely linked to an unusual isoform of beta-spectrin. PMID:2645300